We are led to question whether the recommended social distancing measures to prevent SARS-CoV-2 transmission could increase the number of other serious instabilities. The breaking of the contagion pathways reduces the sharing of microorganisms between people, thus favoring dysbiosis, which, in turn, may increase the poor prognosis of the disease. #covid #microbiome #dysbiosis Célia P. F. Domingues, João S. Rebelo, Francisco Dionisio, Ana Botelho, Teresa Nogueira. The Social Distancing Imposed To Contain COVID-19 Can Affect Our Microbiome: a Double-Edged Sword in Human Health. mSphere, 2020; 5 (5) DOI: 10.1128/mSphere.00716-20 https://msphere.asm.org/content/5/5/e00716-20
Selenium and COVID-19 A Strong Survival Correlation & New Drug Discoveries
Quote “Our results show an association between the reported cure rates for COVID-19 and selenium status. These data are consistent with the evidence of the antiviral effects of selenium from previous studies”
#COVID19 #SARCOV2 #SELENIUM
Margaret P Rayman, Ramy Saad, Kate Bennett, Ethan Will Taylor, Jinsong Zhang. Association between regional selenium status and reported outcome of COVID-19 cases in China. The American Journal of Clinical Nutrition, 2020; DOI: 10.1093/ajcn/nqaa095
Onat Kadioglu, Mohamed Saeed, Henry Johannes Greten, Thomas Efferth. Identification of novel compounds against three targets of SARS CoV-2 coronavirus by combined virtual screening and supervised machine learning. Bulletin of the World Health Organization, March 21, 2020; DOI: 10.2471/BLT.20.255943
Selenium, recovery, covid-19, sars-cov-2, honeysuckle, hepatitis C drugs, honey suckle, selenium levels, virus, virus mutation, recovery rates, simeprevir, paritaprevir, grazoprevir, velpatasvir, selenoproteins, selenium status, immune system, viral mutation, cure rate, viral pathogenicity, mortality
COVID-19 Updated Nutritional Supplement Research
Dietary supplements an important weapon for fighting off COVID-19
Optimal Nutritional Status for a Well-Functioning Immune System Is an Important Factor to Protect against Viral Infections Nutrients 2020, 12(4), 1181; https://doi.org/10.3390/nu12041181
Ayurveda and yoga for COVID-19 prevention
Public Health Approach of Ayurveda and Yoga for COVID-19 Prophylaxis Published Online:20 Apr 2020https://doi.org/10.1089/acm.2020.0129
#Ashwagandha, #Dietarysupplements, #sars-cov-2
Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area JAMA. Published online April 22, 2020. doi:10.1001/jama.2020.6775
Annals of Internal Medicine
Ayurveda, sars-cov-2, yoga, dietary supplements, immune system, , dosage, zinc, omega-3, dha, epa, nutritional status, mechanical ventilator, mortality, vitamin e, SARS coronavirus 2, Prophylaxis, immune system; viral infection; influenza; COVID-19; micronutrients, vitamins, omega-3 fatty acids, minerals, vitamin C, vitamin D, influenza, flu, virus,
Creatine powers the immune system to fight cancer
The energy-buffering function of creatine certainly goes beyond regulating CD8 T cells. In CrT-KO mice, we have observed the hyporesponsiveness of multiple immune cells in various mouse tumor models. It is also likely that creatine regulates immune reactions to multiple diseases beyond cancer, such as infections and autoimmune diseases (Riesberg et al., 2016). Studying the roles of creatine in modulating various immune cells under different health and disease conditions will be interesting topics for future research.
Stefano Di Biase, Xiaoya Ma, Xi Wang, Jiaji Yu, Yu-Chen Wang, Drake J. Smith, Yang Zhou, Zhe Li, Yu Jeong Kim, Nicole Clarke, Angela To, Lili Yang. Creatine uptake regulates CD8 T cell antitumor immunity. The Journal of Experimental Medicine, 2019; jem.20182044 DOI: 10.1084/jem.20182044
#creatine #tumors #cancer
100% Cure Rate Pancreatic Cancer Experimental Study Animal Model
A research team reports that combining a type of radiation therapy with immunotherapy not only cures pancreatic cancer in mice, but appears to reprogram the immune system to create an ‘immune memory’ in the same way that a vaccine keeps the flu away. The result is that the combination treatment also destroyed pancreatic cells that had spread to the liver, a common site for metastatic disease.
#il-12 #sbrt #pancraticcancercure
Bradley N. Mills, Kelli A. Connolly, Jian Ye, Joseph D. Murphy, Taylor P. Uccello, Booyeon J. Han, Tony Zhao, Michael G. Drage, Aditi Murthy, Haoming Qiu, Ankit Patel, Nathania M. Figueroa, Carl J. Johnston, Peter A. Prieto, Nejat K. Egilmez, Brian A. Belt, Edith M. Lord, David C. Linehan, Scott A. Gerber. Stereotactic Body Radiation and Interleukin-12 Combination Therapy Eradicates Pancreatic Tumors by Repolarizing the Immune Microenvironment. Cell Reports, 2019; 29 (2): 406 DOI: 10.1016/j.celrep.2019.08.095
Pancreatic cancer, il-12, sbrt, stereotactic body radiotherapy, pancreas, cancer, aggressive, advanced, study, CD8, treatment, immune system, vaccine, cancer vaccine, liver cancer, metastatic
Elderberry shown to fight Influenza at multiple stages
The phytochemicals from the elderberry juice were shown to be effective at stopping the virus infecting the cells, however to the surprise of the researchers they were even more effective at inhibiting viral propagation at later stages of the influenza cycle when the cells had already been infected with the virus.
#Elderberry #Influenza # anthocyanidin
Golnoosh Torabian, Peter Valtchev, Qayyum Adil, Fariba Dehghani. Anti-influenza activity of elderberry (Sambucus nigra). Journal of Functional Foods, 2019; 54: 353 DOI: 10.1016/j.jff.2019.01.031
Bacteria can evolve rapidly to adapt to environmental change. When the “environment” is the immune response of an infected host, this evolution can turn harmless bacteria into life-threatening pathogens. A study published on December 12 in PLOS Pathogens provides insight into how this happens.
Isabel Gordo and colleagues from the Instituto Gulbenkian de Ciencia in Oeira, Portugal, have for the first time devised an experimental system to observe and study the evolution of bacteria in response to encounters with cells of the mammalian immune system. They found that in less than 500 bacterial generations (or 30 days), the bacteria became more resistant to being killed by immune cells and acquired the ability to cause disease in mice. Continue reading “From friend to foe: How benign bacteria evolve to virulent pathogens”
In this Issue:
1. Amino acid with promising anti-diabetic effects
2. Substance that gives grapefruit its flavor and aroma could give insect pests the boot
3. New study discovers copper destroys highly infectious norovirus
4. Codeine could increase users’ sensitivity to pain
5. Research treats the fungus among us with nontoxic medicinal compound
6. Diets Low in Polyunsaturated Fatty Acids May Be a Problem for Youngsters
7. Obese stomachs tell us diets are doomed to fail
8. Red grapes, blueberries may enhance immune function
9. Can vitamin B supplements help stave off stroke?
Health Research Report
164th Issue Date 21 SEP 2013
Compiled By Ralph Turchiano
ANN ARBOR—It’s been known for decades that animals such as chimpanzees seek out medicinal herbs to treat their diseases. But in recent years, the list of animal pharmacists has grown much longer, and it now appears that the practice of animal self-medication is a lot more widespread than previously thought, according to a University of Michigan ecologist and his colleagues.
Animals use medications to treat various ailments through both learned and innate behaviors. The fact that moths, ants and fruit flies are now known to self-medicate has profound implications for the ecology and evolution of animal hosts and their parasites, according to Mark Hunter, a professor in the Department of Ecology and Evolutionary Biology and at the School of Natural Resources and Environment.
In addition, because plants remain the most promising source of future pharmaceuticals, studies of animal medication may lead the way in discovering new drugs to relieve human suffering, Hunter and two colleagues wrote in a review article titled “Self-Medication in Animals,” to be published online today in the journal Science.
“When we watch animals foraging for food in nature, we now have to ask, are they visiting the grocery store or are they visiting the pharmacy?” Hunter said. “We can learn a lot about how to treat parasites and disease by watching other animals.”
Much of the work in this field has focused on cases in which animals, such as baboons and woolly bear caterpillars, medicate themselves. One recent study has suggested that house sparrows and finches add high-nicotine cigarette butts to their nests to reduce mite infestations.
But less attention has been given to the many cases in which animals medicate their offspring or other kin, according to Hunter and his colleagues. Wood ants incorporate an antimicrobial resin from conifer trees into their nests, preventing microbial growth in the colony. Parasite-infected monarch butterflies protect their offspring against high levels of parasite growth by laying their eggs on anti-parasitic milkweed.
Hunter and his colleagues suggest that researchers in the field should “de-emphasize the ‘self’ in self-medication” and base their studies on a more inclusive framework.
“Perhaps the biggest surprise for us was that animals like fruit flies and butterflies can choose food for their offspring that minimizes the impacts of disease in the next generation,” Hunter said. “There are strong parallels with the emerging field of epigenetics in humans, where we now understand that dietary choices made by parents influence the long-term health of their children.”
The authors argue that animal medication has several major consequences on the ecology and evolution of host-parasite interactions. For one, when animal medication reduces the health of parasites, there should be observable effects on parasite transmission or virulence.
For example, when gypsy moth caterpillars consume foliage high in certain toxic compounds, transmission of viruses between the caterpillars is reduced, facilitating moth outbreaks.
In addition, animal medication should affect the evolution of animal immune systems, according to Hunter and his colleagues. Honeybees are known to incorporate antimicrobial resins into their nests. Analysis of the honeybee genome suggests that they lack many of the immune-system genes of other insects, raising the possibility that honeybees’ use of medicine has been partly responsible—or has compensated—for a loss of other immune mechanisms.
The authors also note that the study of animal medication will have direct relevance for human food production. Disease problems in agricultural organisms can worsen when humans interfere with the ability of animals to medicate, they point out.
For example, increases in parasitism and disease in honeybees can be linked to selection by beekeepers for reduced resin deposition by their bees. A reintroduction of such behavior in managed bee colonies would likely have great benefits for disease management, the authors say.
The first author of the Science paper is Jacobus de Roode of Emory University. The other author is Thierry Lefevre of the Institut de Recherche pour le Developpement in France.
Designer bacteria may lead to better vaccines
61 new strains of genetically engineered bacteria may improve the efficacy of vaccines for diseases such as flu, pertussis, cholera and HPV
AUSTIN, Texas — Researchers at The University of Texas at Austin have developed a menu of 61 new strains of genetically engineered bacteria that may improve the efficacy of vaccines for diseases such as flu, pertussis, cholera and HPV.
The strains of E. coli, which were described in a paper published this month in the journal PNAS, are part of a new class of biological “adjuvants” that is poised to transform vaccine design. Adjuvants are substances added to vaccines to boost the human immune response.
“For 70 years the only adjuvants being used were aluminum salts,” said Stephen Trent, associate professor of biology in the College of Natural Sciences. “They worked, but we didn’t fully understand why, and there were limitations. Then four years ago the first biological adjuvant was approved by the Food and Drug Administration. I think what we’re doing is a step forward from that. It’s going to allow us to design vaccines in a much more intentional way.”
Adjuvants were discovered in the early years of commercial vaccine production, when it was noticed that batches of vaccine that were accidentally contaminated often seemed to be more effective than those that were pure.
“They’re called the ‘dirty little secret’ of immunology,” said Trent. “If the vials were dirty, they elicited a better immune response.”
What researchers eventually realized was that they could produce a one-two punch by intentionally adding their own dirt (adjuvant) to the mix. The main ingredient of the vaccine, which was a killed or inactivated version of the bacteria or virus that the vaccine was meant to protect against, did what it was supposed to do. It “taught” the body’s immune system to recognize it and produce antibodies in response to it.
The adjuvant amplifies that response by triggering a more general alarm, which puts more agents of the immune system in circulation in the bloodstream, where they can then learn to recognize the key antigen. The result is an immune system more heavily armed to fight the virus or bacteria when it encounters it in the future.
For about 70 years the adjuvant of choice, in nearly every vaccine worldwide, was an aluminum salt. Then in 2009, the FDA approved a new vaccine for human papillomavirus (HPV). It included a new kind of adjuvant that’s a modified version of an endotoxin molecule.
These molecules, which can be dangerous, appear on the cell surface of a wide range of bacteria. As a result, humans have evolved over millions of years to detect and respond to them quickly. They trigger an immediate red alert.
“In some of its forms an endotoxin can kill you,” said Trent. “But the adjuvant, which is called MPL, is a very small, carefully modified piece of it, so it’s able to trigger the immune response without overdoing it.”
What Trent and his colleagues have done is expand on that basic premise. Rather than just work with an inert piece of endotoxin, they’ve engineered E. coli bacteria to express the endotoxin in many configurations on the cell surface.
“These 61 E. coli strains each have a different profile on their surface,” said Brittany Needham, a doctoral student in Trent’s lab and the first author on the paper. “In every case the surface structure of the endotoxin is safe, but it will interact with the immune system in a range of ways. Suddenly we have a huge potential menu of adjuvants to test out with different kinds of vaccines.”
One form might work better with cholera vaccine, another with pertussis (whooping cough) and another with a future HIV vaccine. Trent, Needham and their colleagues should be able to fine-tune the adjuvants with increasing precision as more E. coli strains are engineered and tested, and as their understanding of how they interact with the immune system deepens.
“I think we’re at the dawn of a new age of vaccine design,” said Trent. “For a long time vaccinology was really a trial-and-error field. It was a black box. We knew certain things worked. We knew certain vaccines had certain side effects. But we didn’t entirely know why. Now that’s changing.”
Trent said that an additional advantage of their system is that the E. coli can be engineered to express key viral and bacterial antigens along with the endotoxin. A single cell could deliver both parts of the one-two punch, or even a one-two-three punch, if antigens from multiple diseases were expressed in a single E. coli.
“It makes possible a vaccine that provides protection from multiple pathogens at the same time,” said Trent.
Trent and his colleagues are working on a second round of designer E. coli. They have also filed a provisional patent on their system and are working with the university to find a corporate partner to pay for clinical trials.
“This is ready to go,” said Trent. “I can’t predict whether it will actually make it to the market. But it’s very similar to the adjuvant that has already been approved, and my instinct is that if a company will undertake to do the trials, it will get approved. A company could call us tomorrow, we could send them a strain, and they could start working.”
Tuesday, Nov. 27, 2012
Writer: James E. Hataway, 706/542-5222, firstname.lastname@example.org Contact: Biao He, 706/542-2855, email@example.com
Athens, Ga. – Researchers at the University of Georgia have discovered that a virus commonly found in dogs may serve as the foundation for the next great breakthrough in human vaccine development.
Although harmless in humans, parainfluenza virus 5, or PIV5, is thought to contribute to upper respiratory infections in dogs, and it is a common target for canine vaccines designed to prevent kennel cough. In a paper published recently in PLOS ONE, researchers describe how this virus could be used in humans to protect against diseases that have eluded vaccine efforts for decades.
“We can use this virus as a vector for all kinds of pathogens that are difficult to vaccinate against,” said Biao He, the study’s principal investigator and professor of infectious diseases in UGA’s College of Veterinary Medicine. “We have developed a very strong H5N1 flu vaccine with this technique, but we are also working on vaccines for HIV, tuberculosis and malaria.”
PIV5 does not cause disease in humans, as our immune system is able to recognize and destroy it. By placing antigens from other viruses or parasites inside PIV5, it effectively becomes a delivery vehicle that exposes the human immune system to important pathogens and allows it to create the antibodies that will protect against future infection.
This approach not only ensures full exposure to the vaccine but also is much safer because it does not require the use of attenuated, or weakened, pathogens. For example, an HIV vaccine delivered by PIV5 would contain only those parts of the HIV virus necessary to create immunity, making it impossible to contract the disease from the vaccine.
“Safety is always our number one concern,” said He, who is also a Georgia Research Alliance distinguished investigator and member of the Faculty of Infectious Diseases. “PIV5 makes it much easier to vaccinate without having to use live pathogens.”
Using viruses as a delivery mechanism for vaccines is not a new technique, but previous efforts have been fraught with difficulty. If humans or animals already possess a strong immunity to the virus used for delivery, the vaccine is unlikely to work, as it will be destroyed by the immune system too quickly.
“Pre-existing immunity to viruses is the main reason most of these vaccines fail,” He said.
But in this latest study, He and his colleagues demonstrate that immunity to PIV5 does not limit its effectiveness as a vaccine delivery mechanism, even though many animals-including humans- already carry antibodies against it.
In their experiments, the researchers found that a single dose inoculation using PIV5 protected mice from the influenza strain that causes seasonal flu. Another single dose experimental vaccine also protected mice from the highly pathogenic and deadly H5N1 virus commonly known as bird flu.
This recent work is a culmination of more than fifteen years of research and experimentation with the PIV5 virus, and He has confidence that it will serve as an excellent foundation for vaccines to treat diseases in both animals and humans.
“I believe we have the best H5N1 vaccine candidate in existence,” He said. “But we have also opened up a big field for a host of new vaccines.”
UGA Faculty of Infectious Diseases The University of Georgia Faculty of Infectious Diseases was created in 2007 to address existing and emerging infectious disease threats more effectively by integrating multidisciplinary research in animal, human and ecosystem health. Researchers from across the university focus on epidemiology, host-pathogen interactions, the evolution of infectious diseases, disease surveillance and predictors and the development of countermeasures such as vaccines, therapeutics and diagnostics. For more information about the Faculty of Infectious Diseases, see fid.ovpr.uga.edu.
UGA College of Veterinary Medicine The UGA College of Veterinary Medicine, founded in 1946, is dedicated to training future veterinarians, to conducting research related to animal and human diseases, and to providing veterinary services for animals and their owners. Research efforts are aimed at enhancing the quality of life for animals and people, improving the productivity of poultry and livestock, and preserving a healthy interface between wildlife and people in the environment they share. The college enrolls 102 students each fall out of more than 800 who apply.
2009 study posted for filing
Contact: Cody Mooneyhan
Federation of American Societies for Experimental Biology
Got zinc? New zinc research suggests novel therapeutic targets
New report in the Journal of Leukocyte Biology suggests that zinc activates a key protein on T cells needed to fight infections
Everyone knows that vitamins “from A to zinc” are important for good health. Now, a new research study in the August 2009 print issue of the Journal of Leukocyte Biology (http://www.jleukbio.org) suggests that zinc may be pointing the way to new therapeutic targets for fighting infections. Specifically, scientists from Florida found that zinc not only supports healthy immune function, but increases activation of the cells (T cells) responsible for destroying viruses and bacteria.
“It has been shown that zinc supplementation significantly reduces the duration and severity of childhood diarrhea, lower respiratory infections, and incidence of malaria in zinc-deficient children,” said report co-author, Robert Cousins, Ph.D., who also is the director of the Center for Nutritional Sciences within the Food Science and Human Nutrition Department at the University of Florida. “Age-related declines in immune function have also been related to zinc deficiency in the elderly.”
Scientists administered either a zinc supplement or a placebo to healthy volunteers to assess the effects of zinc on T cell activation. After isolating the T cells from the blood, scientists then simulated infection in laboratory conditions. Results showed that T cells taken from the zinc-supplemented group had higher activation than those from the placebo group. Specifically, cell activation stimulated the zinc transporter in T cells called “ZIP8,” which transports stored zinc into the cell cytoplasm where it then alters the expression of a T cell protein in a way needed to fight infections.
“As the debate over zinc supplementation in healthy individuals continues,” said John Wherry, Ph.D., Deputy Editor of the Journal of Leukocyte Biology, “studies like this help shed light on how zinc may enhance the ability of our immune systems to fight off foreign invaders. Equally important, this work points toward new possible targets for entirely new drugs to help augment immune function and prevent or stop infections that might be resistant to traditional antibiotics.”
The Journal of Leukocyte Biology (http://www.jleukbio.org) publishes peer-reviewed manuscripts on original investigations focusing on the cellular and molecular biology of leukocytes and on the origins, the developmental biology, biochemistry and functions of granulocytes, lymphocytes, mononuclear phagocytes and other cells involved in host defense and inflammation. The Journal of Leukocyte Biology is published by the Society for Leukocyte Biology.
Details: Tolunay B. Aydemir, Juan P. Liuzzi, Steve McClellan, and Robert J. Cousins Zinc transporter ZIP8 (SLC39A8) and zinc influence IFN- expression in activated human T cells. J Leukoc Biol 2009 86: 337�. http://www.jleukbio.org/cgi/content/abstract/86/2/337
2009 study posted for filing
Exposure to dioxins during pregnancy harms the cells in rapidly-changing breast tissue, which may explain why some women have trouble breastfeeding or don’t produce enough milk, according to a University of Rochester Medical Center study.
Researchers believe their findings, although only demonstrated in mice at this point, begin to address an area of health that impacts millions of women but has received little attention in the laboratory, said corresponding author B. Paige Lawrence, Ph.D., associate professor of Environmental Medicine and of Microbiology and Immunology at URMC.
“Estimates are that three to six million mothers worldwide are either unable to initiate breastfeeding or are unable to produce enough milk to nourish their infants,” Lawrence said. “But the cause of this problem is unclear, though it has been suggested that environmental contaminants might play a role. We showed definitively that a known and abundant pollutant has an adverse effect on the way mammary glands develop during pregnancy.”
Dioxins are generated mostly by the incineration of municipal and medical waste, especially certain plastics. Most people are exposed through diet. Dioxins get into the food supply when air emissions settle on farm fields and where livestock graze. Fish also ingest dioxins and related pollutants from contaminated waters. When humans take in dioxin – most often through meat, dairy products, fish and shellfish – the toxin settles in fatty tissues; natural elimination takes place very slowly. The typical human exposure is a daily low dose, which has been linked to possible impairment of the immune system and developing organs.
In 2004 Lawrence’s laboratory made the novel discovery that dioxin impairs the normal development of mammary glands during pregnancy. However, the underlying mechanisms were unclear, as was the extent of injury and whether exposure during certain stages of pregnancy had more or less of an impact on milk production.
This week, in an online report in Toxicological Sciences, researchers showed that dioxin has a profound effect on breast tissue by causing mammary cells to stop their natural cycle of proliferation as early as six days into pregnancy, and lasting through mid-pregnancy. In tissue samples from mice, exposure to dioxin caused a 50-percent decrease in new epithelial cells. This is important, Lawrence said, because mammary glands have a high rate of cell proliferation, especially during early to mid-pregnancy when the most rapid development of the mammary gland occurs.
Researchers also found that dioxin altered the induction of milk-producing genes, which occurs around the ninth day of pregnancy, and decreased the number of ductal branches and mature lobules in the mammary tissue.
The timing of dioxin exposure also seemed to be significant, the study noted. For example, when exposure occurs very early in pregnancy but not later, lab experiments showed that sometimes the mammary glands can partially recover from the cellular injury. However, although it is important to understand timing of exposure for research purposes, it is irrelevant for humans, who cannot really control their exposure to dioxins, Lawrence said.
“Our goal is not to find a safe window of exposure for humans, but to better understand how dioxins affect our health,” she said. “The best thing people who are concerned about this can do is think about what you eat and where your food comes from. We’re not suggesting that we all become vegans — but we hope this study raises awareness about how our food sources can increase the burden of pollutants in the body. Unfortunately, we have very little control over this, except perhaps through the legislative process.”
Much of Lawrence’s research focuses on a transcription factor known as aryl hydrocarbon receptor, or AhR.When pollutants enter the body they bind to AhR, which then turns on certain genes responsible for detoxification. By using dioxin to activate AhR, researchers have learned that dioxin impairs the ability to fight off infection. The link between dioxin and the immune system is still being studied, but meanwhile researchers looked further at the mammary tissue after observing coincidentally that cells involved in milk production were sustaining so much damage that rodents could not nourish their offspring.
The next step is to understand what controls the differentiation process. An important question to answer, Lawrence said, is whether the toxic harm is occurring directly in the breast, or if it occurs throughout the entire body but has a unique manifestation in the fatty mammary tissue.
The URMC research group is also studying a possible connection between dioxin and breast cancer.Their hypothesis is that dioxin exposure in some people might cancel the general protection that pregnancy has on breast tissue against breast cancer.
The research was supported by grants from the National Institutes of Health and the URMC Environmental Health Sciences Center, as well as the Art BeCAUSE Foundation of Boston, which funds breast-cancer related research.
Researchers Identify How Mosquito Immune System Attacks Specific Infections
Researchers at the Johns Hopkins Bloomberg School of Public Health have determined a new mechanism by which the mosquitoes’ immune system can respond with specificity to infections with various pathogens, including the parasite that causes malaria in humans, using one single gene. Unlike humans and other animals, insects do not make antibodies to target specific infections. According to the Johns Hopkins researchers, mosquitoes use a mechanism known as alternative splicing to arrange different combinations of binding domains, encoded by the same AgDscam gene, into protein repertoires that are specific for different invading pathogens. The researchers’ findings were published October 18 in the journal Cell Host & Microbe and could lead to new ways to prevent the spread of a variety of mosquito born illnesses.
Mosquitoes and other insects use their primitive innate immune systems to successfully fight infections with a broad spectrum of viruses, bacteria, fungi and parasites, despite the lack of antibodies that are part of the more sophisticated human immune system. The effectiveness of the human immune system is to a large degree based on the ability to produce an enormous variety of antibodies containing different immunoglobulin domains that can specifically tag and label a pathogen for destruction. This great variety of pathogen-binding antibodies is achieved by combining different immunoglobulin gene segments and further mutate them through mechanisms called somatic recombination and hypermutation. While mosquitoes also have genes encoding immunoglobulin domains, they lack these specific mechanisms to achieve pathogen recognition diversity.
The Johns Hopkins researchers discovered a different way by which mosquitoes can combine immunoglobulin domains of a single gene called AgDscam (Anopheles gambiae Down Syndrome Cell Adhesion Molecule) to produce a variety of pathogen-binding proteins. The AgDscam gene is subjected to a mechanism called alternative splicing that combines different immunoglobulin domains into mature AgDscam proteins, depending on which pathogen has infected the mosquito. The researchers showed that this alternative splicing is guided by the immune signal transducing pathways (analogous to electrical circuits) that they previously demonstrated to activate defenses against different malaria parasites and other pathogens. While alternative splicing of the AgDscam gene does not nearly achieve the degree of pathogen recognition diversity of human antibodies, it does nevertheless vastly increase the variety of pathogen binding molecules.
“Using antibodies to fight infection is like fishing with a harpoon—it’s very targeted. The mosquito’s innate immune system is more like fishing with a net—it catches a bit of everything,” explained George Dimopoulos, PhD, senior investigator of the study and professor with the Johns Hopkins Malaria Research Institute. “However, we discovered that immune pathway-guided alternative splicing of the AgDscam gene renders the mosquito’s immune net, so to speak, more specific than previously suspected. The mosquito’s immune system can come up with approximately 32,000 AgDscam protein combinations to target infections with greater specificity.”
Dimopoulos and his group are developing a malaria control strategy based on mosquitoes that have been genetically modified to possess an enhanced immune defense against the malaria parasite Plasmodium. One obstacle to this approach is the great variety of Plasmodium strains that may interact somewhat differently with the mosquito’s immune system.
“Some of these strains may not be detected by the engineered immune system proteins that mediate their killing. Our new discovery may provide the means to create genetically modified mosquitoes that can target a broader variety of parasite strains, like casting a net rather than shooting with a harpoon,” said Dimopoulos.
Malaria kills more than 800,000 people worldwide each year. Many are children.
“Anopheles NF-kB –Regulated Splicing Factors Direct Pathogen-Specific Repertoires of the Hypervariable Pattern Recognition Receptor AgDscam” was written by Yuemei Dong, Chris M. Cirimotich, Andrew Pike, Ramesh Chandra and George Dimopoulos.
The research was supported by grants from the National Institutes of Health/National Institute of Allergy and Infectious Disease, the Calvin A. and Helen H. Lang Fellowship, and the Johns Hopkins Malaria Research Institute.
Media contact: Tim Parsons, director of Public Affairs, at 410-955-7619 or firstname.lastname@example.org.
2009 report posted for filing
Saranac Lake, N.Y., -Dr. Marcia Blackman and her research team at the Trudeau Institute have followed up on an intriguing report(1)published in the journal Nature in May 2007 by Dr. Herbert Virgin, et al., showing that mice persistently infected with certain forms of herpesvirus, which can establish lifelong latent infections, are resistant to infection with bacterial pathogens.
Although herpesvirus infections are generally considered undesirable and can be associated with declining immune function in the elderly or the development of a variety of tumors later in life, the Virgin report raised the unexpected possibility that they may also be beneficial.
Dr. Blackman’s research has now confirmed Dr. Virgin’s findings, but with some further refinements about herpes’ roles in preventing other infections: “We discovered that the effect of herpesvirus infection is transient, lasting only a few months. Interestingly, although the effect was shown by the Virgin group to be dependent on establishing a latent infection, it wanes despite lifelong latency.”
Recognizing that her data had implications for the interpretation of Dr. Virgin’s data, Dr. Blackman shared her findings with the Virgin group prior to publication. This led to an interesting exchange between the two labs in the form of letters to the editor regarding the potential benefits of a transient protective effect. The letters will be published concurrently with Blackman’s data in the February issue of Viral Immunology (Vol. 22, No.1). The scientists agree that even short-acting protection, especially during childhood, might have long-lasting implications in terms of survival rates.
A major point of discussion between the two groups concerned the implications of such research for the development of vaccines against herpesvirus infections. Dr. Virgin suggested that “decreased infection may be associated with unintended negative consequences for vaccinated individuals.” In response, Dr. Blackman argues that possible transient protective effects did not outweigh the already recognized pathological consequences of herpesvirus infection. Both groups agreed that the protective effects of herpesvirus infections merit further study.
Importantly, both groups hope their observations will stimulate epidemiological and clinical studies to determine whether herpesvirus infections really protect humans against bacterial diseases.
(1)“Herpesvirus latency confers symbiotic protection from bacterial infection,” NATURE, Vol. 447, pp. 326-29; May 17, 2007.
Zinc deficiency mechanism linked to aging, multiple diseases
CORVALLIS, Ore. – A new study has outlined for the first time a biological mechanism by which zinc deficiency can develop with age, leading to a decline of the immune system and increased inflammation associated with many health problems, including cancer, heart disease, autoimmune disease and diabetes.
The research was done by scientists in the Linus Pauling Institute at Oregon State University and the OSU College of Public Health and Human Sciences. It suggests that it’s especially important for elderly people to get adequate dietary intake of zinc, since they may need more of it at this life stage when their ability to absorb it is declining.
About 40 percent of elderly Americans and as many as two billion people around the world have diets that are deficient in this important, but often underappreciated micronutrient, experts say.
The study was published in the Journal of Nutritional Biochemistry, based on findings with laboratory animals. It found that zinc transporters were significantly dysregulated in old animals. They showed signs of zinc deficiency and had an enhanced inflammatory response even though their diet supposedly contained adequate amounts of zinc.
When the animals were given about 10 times their dietary requirement for zinc, the biomarkers of inflammation were restored to those of young animals.
“The elderly are the fastest growing population in the U.S. and are highly vulnerable to zinc deficiency,” said Emily Ho, an LPI principal investigator and associate professor in OSU School of Biological and Population Health Sciences. “They don’t consume enough of this nutrient and don’t absorb it very well.”
“We’ve previously shown in both animal and human studies that zinc deficiency can cause DNA damage, and this new work shows how it can help lead to systemic inflammation,” Ho said.
“Some inflammation is normal, a part of immune defense, wound healing and other functions,” she said. “But in excess, it’s been associated with almost every degenerative disease you can think of, including cancer and heart disease. It appears to be a significant factor in the diseases that most people die from.”
As a result of this and what is now know about zinc absorption in the elderly, Ho said that she would recommend all senior citizens take a dietary supplement that includes the full RDA for zinc, which is 11 milligrams a day for men and 8 milligrams for women. Zinc can be obtained in the diet from seafood and meats, but it’s more difficult to absorb from grains and vegetables – a particular concern for vegetarians.
“We found that the mechanisms to transport zinc are disrupted by age-related epigenetic changes,” said Carmen Wong, an OSU research associate and co-author of this study. “This can cause an increase in DNA methylation and histone modifications that are related to disease processes, especially cancer. Immune system cells are also particularly vulnerable to zinc deficiency.”
Research at OSU and elsewhere has shown that zinc is essential to protect against oxidative stress and help repair DNA damage. In zinc deficiency, the risk of which has been shown to increase with age, the body’s ability to repair genetic damage may be decreasing even as the amount of damage is going up.
Medical tests to determine zinc deficiency are rarely done, scientists say, and are not particularly accurate even if they are done. The best approach is to assure adequate intake of the nutrient through diet or supplements, they said, especially in the elderly.
Even though elderly people have less success in absorbing zinc, the official RDA for them is the same as in younger adults. That issue should be examined more closely, Ho said.
Levels of zinc intake above 40 milligrams per day should be avoided, researchers said, because at very high levels they can interfere with absorption of other necessary nutrients, including iron and copper.
These studies were supported by the National Institutes of Health and other agencies.
The upside to allergies: cancer prevention
A new article in the December issue of The Quarterly Review of Biology provides strong evidence that allergies are much more than just an annoying immune malfunction. They may protect against certain types of cancer.
The article, by researchers Paul Sherman, Erica Holland and Janet Shellman Sherman from Cornell University, suggests that allergy symptoms may protect against cancer by expelling foreign particles, some of which may be carcinogenic or carry absorbed carcinogens, from the organs most likely to come in with contact them. In addition, allergies may serve as early warning devices that let people know when there are substances in the air that should be avoided.
Medical researchers have long suspected an association between allergies and cancer, but extensive study on the subject has yielded mixed, and often contradictory, results. Many studies have found inverse associations between the two, meaning cancer patients tended to have fewer allergies in their medical history. Other studies have found positive associations, and still others found no association at all.
In an attempt to explain these contradictions, the Cornell team reexamined nearly 650 previous studies from the past five decades. They found that inverse allergy-cancer associations are far more common with cancers of organ systems that come in direct contact with matter from the external environment—the mouth and throat, colon and rectum, skin, cervix, pancreas and glial brain cells. Likewise, only allergies associated with tissues that are directly exposed to environmental assaults—eczema, hives, hay fever and animal and food allergies—had inverse relationships to cancers.
Such inverse associations were found to be far less likely for cancers of more isolated tissues like the breast, meningeal brain cells and prostate, as well as for myeloma, non-Hodgkins lymphoma and myelocytic leukemia.
The relationship between asthma and lung cancer, however, is a special case. A majority of the studies that the Cornell team examined found that asthma correlates to higher rates of lung cancer. “Essentially, asthma obstructs clearance of pulmonary mucous, blocking any potentially prophylactic benefit of allergic expulsion,” they explain. By contrast, allergies that affect the lungs other than asthma seem to retain the protective effect.
So if allergies are part of the body’s defense against foreign particle invaders, is it wise to turn them off with antihistamines and other suppressants? The Cornell team says that studies specifically designed to answer this question are needed.
“We hope that our analyses and arguments will encourage such cost/benefit analyses,” they write. “More importantly, we hope that our work will stimulate reconsideration…of the current prevailing view … that allergies are merely disorders of the immune system which, therefore, can be suppressed with impunity.”
Sherman, Paul W., Erica Holland, Janet Shellman Sherman, “Allergies: Their Role In Cancer Prevention,” The Quarterly Review of Biology December 2008
Since 1926, The Quarterly Review of Biology has been dedicated to providing insightful historical, philosophical, and technical treatments of important biological topics
ScienceDaily (Sep. 17, 2012) — Research carried out at the University of South Carolina has identified novel mechanisms through which dioxin, a well-known environmental contaminant, can alter physiological functions, according to a study published online in the journal PLOS ONE.
The research team, which included Narendra Singh, Mitzi Nagarkatti and Prakash Nagarkatti of the USC School of Medicine, demonstrated that exposure to dioxin (TCDD) during pregnancy in an experimental mouse model can cause significant toxicity to the fetus, and specifically to the organs that produce the immune cells that fight infections. They found that dioxin alters small molecules called microRNAs, which can affect the expression of a large number of genes.
The study examined over 608 microRNAs, and 78 of these were significantly altered following exposure to dioxin. On the basis of the pattern of changes in these molecules, the team was also able to predict that dioxin can alter several genes that regulate cancer. Many other physiological systems were also affected, including those involved in reproductive, gastrointestinal, hematological, inflammation, renal and urological diseases as well as genetic, endocrine and developmental disorders.
Dioxin is a highly toxic chemical produced as a byproduct of industrial processes, such as the manufacture of herbicides or pesticides or the bleaching of paper. Because it degrades slowly in the environment and is soluble in fats, dioxin can bio-accumulate in the food chain and is often found in high concentrations in the milk and fat of animals in contaminated regions.
“Our results lend more credence to the hypothesis that fetal exposure to environmental contaminants can have life-long effects,” said Mitzi Nagarkatti. “Prenatal damage to the expression of microRNAs in the immune system could well impact the adult immune response.”
The research was supported in part by the National Institutes of Health (R01ES09098, P01AT003961, R01AT006888, R01ES019313, R01MH094755) and the Veterans Administration (VA Merit Award 1I01BX001357)
Natural Killer (NK) cells defend the body against infectious diseases and cancer by recognizing and killing stressed or infected cells and patients with NK deficiencies are susceptible to severe viral infections. In this issue of the Journal of Clinical Investigation, researchers at Baylor College of Medicine report on a patient with an NK cell deficiency caused by a mutation in CD16, which codes for a protein on the surface of NK cells that recognizes antibodies. To determine the exact role of CD16 in NK cell cytotoxicity, Jordan Orange and colleagues studied the effect of mutant CD16 in a human NK cell line. The mutant CD16 was unable to interact with another NK cell protein, CD2, which is required for cytotoxic activity in NK cells. Patients carrying this mutation were highly susceptible to viral infection. This study identifies a potential cellular mechanism that underlies human congenital immunodeficiency.
Human immunodeficiency-causing mutation defines CD16 in spontaneous NK cell cytotoxicity
Baylor College of Medicine, Houston, TX, USA
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View this article at: http://www.jci.org/articles/view/64837?key=c3d74ae1bcfb3e9124da
|IMAGE:Animal sciences professor Rodney Johnson, and graduate student Saebyeol Jang found that a plant flavonoid, luteolin, inhibited a key pathway in the inflammatory response of microglia.|
Researchers at the University of Illinois report this week that a plant compound found in abundance in celery and green peppers can disrupt a key component of the inflammatory response in the brain. The findings have implications for research on aging and diseases such as Alzheimer’s and multiple sclerosis.
The study appears this week in Proceedings of the National Academy of Sciences.
Inflammation can be a blessing or a blight. It is a critical part of the body’s immune response that in normal circumstances reduces injury and promotes healing. When it goes awry, however, the inflammatory response can lead to serious physical and mental problems.
Inflammation plays a key role in many neurodegenerative diseases and also is implicated in the cognitive and behavioral impairments seen in aging.
The new study looked at (LOO-tee-OH-lin), a plant flavonoid known to impede the inflammatory response in several types of cells outside the central nervous system. The purpose of the study was to determine if luteolin could also reduce inflammation in the brain, said animal sciences professor and principal investigator Rodney Johnson.
“One of the questions we were interested in is whether something like luteolin, or other bioactive food components, can be used to mitigate age-associated inflammation and therefore improve cognitive function and avoid some of the cognitive deficits that occur in aging,” Johnson said.
The researchers first studied the effect of luteolin on microglia. These brain cells are a key component of the immune defense. When infection occurs anywhere in the body, microglia respond by producing inflammatory cytokines, chemical messengers that act in the brain to orchestrate a whole-body response that helps fight the invading microorganism.
This response is associated with many of the most obvious symptoms of illness: sleepiness, loss of appetite, fever and lethargy, and sometimes a temporary diminishment of learning and memory. Neuroinflammation can also lead some neurons to self-destruct, with potentially disastrous consequences if it goes too far.
Graduate research assistant Saebyeol Jang studied the inflammatory response in microglial cells. She spurred inflammation by exposing the cells to lipopolysaccharide (LPS), a component of the cell wall of many common bacteria.
Those cells that were also exposed to luteolin showed a significantly diminished inflammatory response. Jang showed that luteolin was shutting down production of a key cytokine in the inflammatory pathway, interleukin-6 (IL-6). The effects of luteolin exposure were dramatic, resulting in as much as a 90 percent drop in IL-6 production in the LPS-treated cells.
“This was just about as potent an inhibition as anything we had seen previously,” Johnson said.
But how was luteolin inhibiting production of IL-6″
Jang began by looking at a class of proteins involved in intracellular signaling, called transcription factors, which bind to specific “promoter” regions on DNA and increase their transcription into RNA and translation into proteins.
Using electromobility shift assays, which measure the binding of transcription factors to DNA promoters, Jang eventually determined that luteolin inhibited IL-6 production by preventing activator protein-1 (AP-1) from binding the IL-6 promoter.
AP-1 is in turn activated by JNK, an upstream protein kinase. Jang found that luteolin inhibited JNK phosphorylation in microglial cell culture. The failure of the JNK to activate the AP-1 transcription factor prevented it from binding to the promoter region on the IL-6 gene and transcription came to a halt.
To see if luteolin might have a similar effect in vivo, the researchers gave mice luteolin-laced drinking water for 21 days before injecting the mice with LPS.
Those mice that were fed luteolin had significantly lower levels of IL-6 in their blood plasma four hours after injection with the LPS. Luteolin also decreased LPS-induced transcription of IL-6 in the hippocampus, a brain region that is critical to spatial learning and memory.
The findings indicate a possible role for luteolin or other bioactive compounds in treating neuroinflammation, Johnson said.
“It might be possible to use flavonoids to inhibit JNK and mitigate inflammatory reactions in the brain,” he said. “Inflammatory cytokines such as interleukin-6 are very well known to inhibit certain types of learning and memory that are under the control of the hippocampus, and the hippocampus is also very vulnerable to the insults of aging,” he said. “If you had the potential to decrease the production of inflammatory cytokines in the brain you could potentially limit the cognitive deficits that result.”
Editor’s note: To reach Rodney Johnson, call 217-333-2118; e-mail: firstname.lastname@example.org.
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By Anthony Bond
PUBLISHED:11:52 EST, 8 September 2012| UPDATED:11:52 EST, 8 September 2012
Scientists have discovered a possible evolutionary explanation for the placebo effect with new evidence suggesting the immune system has an on-off switch to save energy.
People who suffer from a weak infection often recover whether they take a medicinal drug or a simple sugar pill – which suggests humans can heal themselves.
But this has begged the question why people need to wait for the placebo before the recovery process from an infection begins.
According to the New Scientist, researchers have now found that something similar to the placebo effect occurs in animals, after studying Siberian hamsters.
If lights above the hamsters laboratory cages mimicked winter, they found the hamsters would not fight the infection.
However, if the lighting was changed to replicate summer conditions, the hamsters mounted a full immune response.
Similar to this, people who think they are taking medicine to treat an illness, but are actually receiving a placebo, can see a response from their immune system twice that than people who take no pills.
The evidence shows that intervention causes a mental response which kicks the immune system into action.
According to Peter Trimmer, a biologist at the University of Bristol, there is an explanation for this.
He suggests that the immune system uses up lots of energy when it is in action. So an animal’s energy reserves cold be severely depleted if the immune system launches a long response to an illness.
If the infection is not likely to causes death, it could be better to wait and see that fighting the illness will not put the animal in other dangers.
Evidence from a computer model designed by Mr Trimmer and his colleagues now supports this evidence.
It found those animals which live in more challenging environments were food was harder to find, they lived longer if they put up with infections rather than launch a response from their immune system.
However, for those animals living in much more favourable conditions, it was better for them to launch a response from their immune systems so they return to health quicker.
This is because in better conditions they have more access to food which provides energy to sustain an immune response
A group of scientists in Italy have developed a vaccine with the potential to protect against fungal pathogens that commonly infect humans, according to a study by Torosantucci and colleagues in the September 5 issue of The Journal of Experimental Medicine. Although these fungi pose little threat to people with healthy immune systems, they can cause fatal infections in those whose immune systems have been weakened by cancer treatments or post-transplant immunosuppressive therapies. No anti-fungal vaccines are currently available.
The new vaccine was made of a sugar-like molecule called beta-glucan that is found on the cell wall of the fungus and that the fungus needs to grow and survive. To induce a robust immune response to the vaccine, the group attached the relatively innocuous beta-glucan to a protein called diptheria toxin that is known to stimulate the immune system and has been used in other human vaccines.
The vaccine protected rodents from fatal fungal infections by triggering the production of anti-beta-glucan antibodies. These antibodies stuck to the invading fungal cell wall and prevented the fungus from growing. The authors now plan to test the vaccine in humans and hope the results are equally promising.
* Repost for Filing
David Hears The Guardian, Tuesday 20 May 2003 10.41 EDT
Viruses and bacteria could be genetically engineered to evade the human immune system, to create a more effective biological weapon, a leading researcher into bio-weapons said yesterday.
In the past 30 years biotechnology has been revolutionised by molecular biology and genetic engineering. These techniques, used to control infectious diseases, can also be used to create more effective biological weapons.
Speaking at the conference on the future of weaponry, Professor Kathryn Nixdorff, of the University of Darmstadt, said that dangerous micro-organisms had already been produced inadvertently during attempts to modify vaccines and viruses.
Russian researchers had created a strain of anthrax bacilli capable of evading immune mechanisms: hamsters injected with the engineered strain were not protected by the usual anthrax vaccine.
Australian researchers trying to develop a vaccine to prevent pregnancy in mice stumbled upon a new and more virulent form of mousepox virus which inhibited the production of a class of lymphocytes needed to combat the infection.
Although humans were not susceptible to infection by mousepox virus there was concern that the human pox virus could be similarly manipulated to make it more deadly.
There were several ways in which modifying micro-organisms had potential military use. Bugs could be given a resistance to antibiotics, they could be made more resistant to the environment and thus longer lasting, and they could be made more lethal.
But she dismissed the suggestion that information gained from the sequencing of the human genome could be used to create a biological weapon specific to a particular racial or ethnic group.
“At present this seems unlikely for several reasons,” she said. “It has been pointed out in several reports that races do not exist from a genetic perspective; there is generally more genetic variation within groups than between groups.
“Indeed, it has been suggested that a re-examination of the race concept is due.”
There was concern that the genome sequence information could be misused. A research team was reported to have built the polio virus from sequence information publicly available, but this was a relatively simple virus and the feat could not be readily repeated with more complex ones
Advantage flu virus
When you are hit with the flu, you know it immediately — fever, chills, sore throat, aching muscles, fatigue. This is your body mounting an immune response to the invading virus. But less is known about what is happening on the molecular level.
Now Northwestern University scientists have discovered one of the ways the influenza virus disarms our natural defense system. The virus decreases the production of key immune system-regulating proteins in human cells that help fight the invader. The virus does this by turning on the microRNAs — little snippets of RNA — that regulate these proteins.
The researchers, led by molecular biologist Curt M. Horvath, are among the first to show the influenza virus can change the expression of microRNA to control immune responses in human lung cells.
The findings reveal a new aspect of the interaction between the influenza virus and its host. Knowing how viruses disable the immune system to wreak havoc in the body will help researchers design therapeutics to preserve the immune response and keep people healthy. The knowledge also may be valuable for future diagnostics.
The study is published by the Journal of Biological Chemistry. The paper will appear in its final form in September.
“It’s a battle of supremacy between virus and host,” said Horvath, the senior author of the paper. “Our goal is to understand how the flu replicates in the host. Now we’ve discovered a new pathway in which the flu controls the immune response, by shutting down vital protein production. With better understanding of this mechanism, one day we may be able to customize therapeutics to target individual flu strains.”
Horvath is the Soretta and Henry Shapiro Research Professor in Molecular Biology and professor of molecular biosciences in the Weinberg College of Arts and Sciences. He also is professor of microbiology-immunology and medicine at the Feinberg School of Medicine.
A microRNA has only 17 to 24 nucleotides, and its function is to dampen or shut down the production of proteins in the body. (Proteins are the workhorses of the cell.) There are hundreds of different types of microRNAs in animals.
It’s been known for many years that when a virus such as influenza infects respiratory cells there is an immediate antiviral response at the cellular level — the first barrier for protecting the body from the virus. Most of the changes that occur are a result of antiviral gene expression.
About 10 years ago, scientists first learned about small RNA pathways called microRNAs, which regulate gene expression. This led Horvath to want to investigate the role of microRNAs in influenza virus infection and determine what they are contributing to the antiviral response. Exactly which genes might the microRNAs be targeting?
In their current study, Horvath and his team used human lung cells, infected them with the influenza A virus and looked to see which microRNAs were activated in response to the virus. They focused on six microRNAs that were found to increase in abundance during flu infection.
The researchers found the virus activated two microRNAs that turned on the genes IRAK1 and MAPK3. This resulted in a decrease in the amount of proteins that help turn on the immune response.
Essentially, the virus uses the cell mechanisms to its advantage, disarming parts of the natural antiviral system. The flu takes over the expression of microRNAs for its own purposes. The flu increases the expression of microRNA, which decreases the amount of protein and diminishes the immune response.
Having identified a specific set of microRNAs whose expression in host respiratory cells is changed by the influenza virus, Horvath next is interested at looking at the clinical outcomes. He is working with Pedro C. Avila, M.D., professor of medicine-allergy-immunology at the Feinberg School to see if the microRNAs are disregulated in patients with influenza.
The title of the paper is “Influenza A Virus Infection of Human Respiratory Cells Induces Primary MicroRNA Expression.” In addition to Horvath, other authors of the paper are first author William A. Buggele and Karen E. Johnson.
Washington, D.C. — A purified extract prepared from a common microbe and delivered to the lungs of laboratory mice in a spray set off a healthy immune response and provided powerful protection against all four major classes of pathogens including those responsible for anthrax and bubonic plague, according to a presentation at the American Society for Cell Biology’s 47th Annual Meeting.
In addition, when the researchers exposed another group of mice to an aerosol of live Streptococcus pneumoniae, the only animals that survived were the ones that had been pre-treated with the spray. A total of 83 percent of these mice survived. None of the untreated animals lived.
The researchers at the M.D. Anderson Cancer Center in Houston developed the spray from a purified extract of the common coccobacillus named Haemophilus influenzae, the cause of ear and sinus infections in human children.
Their “aerosolized lung innate immune stimulant,” as the scientists have named the spray treatment, could benefit immune-compromised patients with cancer, HIV or other diseases as well as emergency workers and the general public facing uncommon threats like an aerosolized bioterror attack or a spreading respiratory epidemic.
According to Brenton Scott who with his postdoctoral advisor, Burton Dickey, developed the spray, the treatment works best if administered four to 24 hours before exposure. Nearly all mice survived when treated before exposure to lethal doses of anthrax, influenza, and the dangerous mold, Aspergillus. But, the treatment also has some benefit when given after exposure. Effectiveness declines over time but seems to last up to five days after a single dose.
The researchers report that protection by stimulant is associated with rapid pathogen killing in the airways, does not depend on recruitment of other immune defense cells such as neutrophils, and correlates with increased levels of antimicrobial polypeptides in the lung lining fluid. The host response is localized to the airways, and safety studies indicate that the treatment causes minimal side effects, even with repeated doses.
Preclinical testing is being completed, and clinical trials are being designed.
* reposted on request
- Maligned molecule found to have beneficial anti-inflammatory effect
PUBLISHED:05:43 EST, 3 August 2012 | UPDATED:06:11 EST, 3 August 2012
A molecule that causes Alzheimer’s disease could reverse paralysis caused by multiple sclerosis (MS), a study has found.
The much-maligned molecule, known as A-beta, has until now been known as the chief culprit behind Alzheimer’s.
But it is also found in multiple-sclerosis lesions, which occur when immune cells invade the brain and spinal cord and attack the insulating coatings of nerve cells.
The nerve signals then get mixed up leading to blindness, loss of muscle control and difficulties with speech, thought and attention
Scientists from Stanford University in the United States wanted to investigate the role the molecule played in MS.
They used a mouse model that mimics several features of the disease – including the autoimmune attack on myelinated sections of the brain. They then injected A-beta into the rodent’s belly.
The scientists had suspected the injection would exacerbate the MS, but the opposite happened.
This shows that when A-beta is injected outside the brain it moderates and can even reverse symptoms of MS and does not cause Alzheimer’s in the mouse.
The researchers believe the startling discovery will open new avenues in the fight against MS, a hugely debilitating condition which affects around 100,000 people in the UK.
Laboratory tests also showed that A-beta countered not only visible symptoms such as paralysis, but also the increase in certain inflammatory molecules that characterises multiple-sclerosis flare-ups.
Lawrence Steinman, an MS expert and lead author of the report, which is published Science Translational Medicine, said: ‘This is the first time A-beta has been shown to have anti-inflammatory properties.’
Lennart Mucke, director of the Gladstone Institute of Neurological Disease in San Francisco and a veteran Alzheimer’s researcher, noted that while A-beta is toxic in the brain, it can have a very different effect elsewhere in the body.
He said: ‘A-beta is made throughout our bodies all of the time. But even though it’s been studied for decades, its normal function remains to be identified.
‘Most intriguing, to me, is this peptide’s potential role in modulating immune activity outside the brain.
‘There probably is a multiple-sclerosis drug in all this somewhere down the line,’ he said.
New research published in the Journal of Leukocyte Biology demonstrates that elevated body temperature plays a vital role on the generation of effective T-cell mediated immune response
Bethesda, MD—With cold and flu season almost here, the next time you’re sick, think twice before taking something for your fever. That’s because scientists have found more evidence that elevated body temperature helps certain types of immune cells to work better. This research is reported in the November 2011 issue of the Journal of Leukocyte Biology (https://www.jleukbio.org).
“An increase in body temperature has been known since ancient times to be associated with infection and inflammation,” said Elizabeth A. Repasky, Ph.D., a researcher involved in the work from the Department of Immunology at the Roswell Park Cancer Institute in Buffalo, New York. “Since a febrile response is highly conserved in nature (even so-called cold blooded animals move to warmer places when they become ill) it would seem important that we immunologists devote more attention to this interesting response.”
Scientists found that the generation and differentiation of a particular kind of lymphocyte, known as a “CD8+ cytotoxic T-cell” (capable of destroying virus-infected cells and tumor cells) is enhanced by mild fever-range hyperthermia. Specifically, their research suggests that elevated body temperature changes the T-cells’ membranes which may help mediate the effects of micro-environmental temperature on cell function. To test this, researchers injected two groups of mice with an antigen, and examined the activation of T-cells following the interaction with antigen presenting cells. Body temperature in half of the mice was raised by 2 degrees centigrade, while the other half maintained a normal core body temperature. In the warmed mice, results showed a greater number of the type of CD8 T-cells capable of destroying infected cells.
“Having a fever might be uncomfortable,” said John Wherry, Ph.D., Deputy Editor of the Journal of Leukocyte Biology, “but this research report and several others are showing that having a fever is part of an effective immune response. We had previously thought that the microbes that infect us simply can’t replicate as well when we have fevers, but this new work also suggests that the immune system might be temporarily enhanced functionally when our temperatures rise with fever. Although very high body temperatures are dangerous and should be controlled, this study shows that we may need to reconsider how and when we treat most mild fevers.”
The Journal of Leukocyte Biology (http://www.jleukbio.org) publishes peer-reviewed manuscripts on original investigations focusing on the cellular and molecular biology of leukocytes and on the origins, the developmental biology, biochemistry and functions of granulocytes, lymphocytes, mononuclear phagocytes and other cells involved in host defense and inflammation. The Journal of Leukocyte Biology is published by the Society for Leukocyte Biology.
Details: Thomas A. Mace, Lingwen Zhong, Casey Kilpatrick, Evan Zynda, Chen-Ting Lee, Maegan Capitano, Hans Minderman, and Elizabeth A. Repasky. Differentiation of CD8+ T cells into effector cells is enhanced by physiological range hyperthermia. J. Leukoc Biol November 2011 90:951-962; doi:10.1189/jlb.0511229 ; http://www.jleukbio.org/content/90/5/951.abstract