Commensal Bacteria Help Fight Viruses

[drmithila]

Healthy humans harbor an enormous and diverse group of bacteria and other bugs that live within their intestines. These microbial partners provide beneficial aid in multiple ways — from helping digest food to the development of a healthy immune system. In a new study published online in the journal Immunity, David Artis, PhD, associate professor of Microbiology, and Michael Abt, PhD, a postdoctoral researcher in the Artis lab, Perelman School of Medicine, University of Pennsylvania, show that commensal bacteria are also essential to fight off viral infections.
“From our studies in mice, we found that signals derived from these beneficial microbes are essential for optimal immune responses to experimental viral infections,” says Artis. “In one way we could consider these microbes as our ‘brothers in arms’ in the fight against infectious diseases.” Artis is also an associate professor of Pathobiology in the Penn School of Veterinary Medicine.
Signals from commensal bacteria influence immune-cell development and susceptibility to infectious or inflammatory diseases. Commensal microbial communities colonize barrier surfaces of the skin, vaginal, upper respiratory, and gastrointestinal tracts of mammals and consist of bacteria, fungi, protozoa, and viruses. The largest and most diverse microbial communities live in the intestine.
Previous studies in patients have associated alterations in bacterial communities with susceptibility to diabetes, obesity, cancer, inflammatory bowel disease, allergy, and other disorders. Despite knowing all of this, exactly how commensal bacteria regulate immunity after being exposed to pathogens is not well understood.
To get a better picture of how these live-in bacteria are beneficial, the Artis lab used several lines of investigation. First, they demonstrated that mice — treated with antibiotics to reduce numbers of commensal bacteria — exhibit an impaired antiviral immune response and a substantially delayed clearance of a systemic virus or influenza virus that infects the airways. What’s more, the treated mice had severely damaged airways and increased rate of death after the experimental influenza virus infection, demonstrating that alterations in commensal bacterial communities can have a negative impact on immunity against viruses.
Next, they profiled the genes that were expressed in immune cells called macrophages isolated from the antibiotic-treated mice. These data revealed a decreased expression of genes associated with antiviral immunity. In addition, macrophages from antibiotic-treated mice showed defective responses to interferons, proteins made and released in response to viruses, bacteria, parasites, or tumor cells. Under normal circumstances, interferons facilitate communication between cells to trigger the immune cells that attack pathogens or tumors. The antibiotic-treated mice also had an impaired capacity to limit viral replication. However, when mice were treated with a compound that restored interferon responsiveness, protective antiviral immunity was re-established.
“It is remarkable that signals derived from one type of microbe, in this case bacteria, can have such a profound effect on immune responses to viruses that are a very different type of microbe,” says first author Abt. “Just like we would set a thermostat to regulate when a heater should come on, our studies indicate that signals derived from commensal bacteria are required to set the activation threshold of the immune system.”
Taken together, these lines of evidence indicate that signals from commensal bacteria beneficially stimulate immune cells in a way that is optimal for antiviral immunity. “Although more work needs to be done, these findings could illuminate new ways to promote better immunity to potentially life-threatening viral infections,” adds Artis.
This research is supported by the National Institutes of Health National Institute of Allergy and Infectious Disease(grants AI061570, AI087990, AI074878, AI095608, AI091759, AI095466, AI071309, AI078897, AI095608, AI083022, AI077098, HHSN266200500030C, T32-AI05528, T32-AI007532, T32-RR007063, K08-DK093784, T32-AI007324); the Irvington Institute Postdoctoral Fellowship of the Cancer Research Institute; the Burroughs Wellcome Fund, the National Institute of Diabetes and Digestive and Kidney Disease Center for the Molecular Studies in Digestive and Liver Disease and the Molecular Pathology and Imaging Core.

 

        

[drmithila]

A new research report published in the Journal of Leukocyte Biology shows how the bacteria known for causing gum disease–Porphyromonas gingivalis–manipulates the body’s immune system to disable normal processes that would otherwise destroy it. Specifically, the report shows that this pathogen prompts the production of the anti-inflammatory molecule Interleukin-10 (IL-10). This, in turn, inhibits the function of T-cells, which would otherwise help to protect the host from this particular microbial infection.

“Since greater than 50 percent of the U.S. population over 50 years-of-age develop adult periodontal disease, we hope that the results of our study will ultimately help in the development of novel treatments that could prevent or ameliorate the chronic infection caused by the pathogen P. gingivalis,'” said Jannet Katz, D.D.S., Ph.D., a researcher involved in the work from the Department of Pediatric Dentistry at the University of Alabama in Birmingham.
To make this discovery, scientists used cells from mice that were exposed to P. gingivalis. One portion of the cells was treated with an inhibiting antibody against IL-10 and the other portion of cells was not treated. All of the cells were then tested for interferon gamma production. An increase of interferon gamma production was seen in the treated cells, but no increase was found in the untreated cells. These findings suggest that the damage done by P. gingivalis happens when the immune cells of the host are first exposed to this pathogen, and further implies that for treatment to be successful, it must be started as early as possible. This study highlights the mechanism by which P. gingivalis can establish a chronic infection in the form of periodontal disease and provides insight into how the disease develops. Results also demonstrate the importance of very early intervention either by eradication of the bacterium with specifically designed therapeutics or by prevention via the development of an effective vaccine.
“Gum diseases and the infections that cause them can be incredibly stubborn and difficult to treat,” said John Wherry, Ph.D., Deputy Editor of the Journal of Leukocyte Biology. “What isn’t as well known is why these infections are so difficult to eradicate. These new studies now demonstrate that these bacteria go beyond merely evading our body’s defenses and actually manipulate our immune systems for their own survival.”

        

[drsushant]

Normal bacteria which live in our mouths provide the catalyst for the development of gum disease, a debilitating condition which leads to painful gums and the loosening of teeth, new research from Queen Mary, University of London has found.
The unexpected finding could pave the way for the development of preventative measures in tackling gum, or periodontal disease*, by manipulating the normal bacteria in the same way that probiotic yoghurt works to protect the intestine.
Researchers at Queen Mary’s Blizard Institute, including Medical Research Council Clinical Research Training Fellow Mark Payne, worked with scientists in the US and published their findings in the journal Cell Host and Microbe.
The scientists introduced the oral bacterium Porphyromonas gingivalis to mice living in two different test conditions. The mice with normal bacteria in their mouths developed periodontal bone loss but the mice raised under germ-free conditions, in the absence of any normal bacteria, remained disease-free.
Professor Mike Curtis, Director of the Blizard Institute and co-author on the paper, said when the oral bacterium P. gingivalis was introduced under normal conditions “it stimulated the growth of normal bugs leading to a large increase in the number of those organisms already there.”
“P. gingivalis was introduced at very low levels yet it had a major affect on both the immune system and the inflammatory system,” he said.
“This oral bacterium only appears in small numbers but appears to have a major influence on the overall ecology. It has a keystone effect in a community — working in the same way that starfish, which have relatively small numbers, control the shell fish communities in the sea.
Professor Curtis said although the findings were encouraging in terms of understanding the way gum disease develops, there was still “some way to go” before there was a similar product on the market for gum disease as a probiotic yoghurt is available for the intestine.
“Now we know that periodontal disease only develops through P. gingivalis interacting with the existing bacteria in our mouths, we need to understand the role played by our normal bacteria in both the development of disease and protection from it,” he said.
“This may then provide the means to develop preventative measures for the disease.”
Professor Farida Fortune, Dean for Dentistry at Queen Mary said the research was encouraging for people who suffer from gum disease which results in bleeding gums and ultimately loose teeth which cause difficulty in both speaking and eating.
“The public still need to be mindful of the way they look after their teeth and gums. People need to pay more attention to their oral hygiene. Their local hygienist, dental therapist and dentist can all assist in teaching them effective cleaning techniques.”
“Just these simple preventative measures, as well as not smoking, will go some way to helping them avoid developing gum disease.”

        

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