Microbiome researchers continue to uncover an increasingly complex interplay between the gut microbiota and the immune system. Now, a team from the City of Hope and the California Institute of Technology has reported that components of certain microorganisms in the gut may bolster the immune system’s ability to fend off fatal brain inflammation caused by a herpes viral infection.
Fatal herpes simplex encephalitis (HSE) results from immune pathology caused by uncontrolled invasion of the brainstem by inflammatory monocytes and neutrophils. The researchers show that the microbial molecule, capsular polysaccharide A (PSA) from Bacteroides fragilis (B. fragilis), promotes a protective, anti-inflammatory response during viral infection.
The research is published in Nature Communications in the paper titled “Bacteroides fragilis polysaccharide A induces IL-10 secreting B and T cells that prevent viral encephalitis.”
“This mouse study shows that B. fragilis PSA can temper the immune system so that infection does not result in an uncontrolled, potentially fatal inflammatory response in the brain,” noted Edouard Cantin, PhD, professor in the department of molecular imaging & therapy, Beckman Research Institute of City of Hope, Duarte, CA.
The researchers, which includes members of the lab of Sarkis Mazmanian, PhD, a professor at the California Institute of Technology, found that B. fragilis‘ bacterial envelope, PSA, brings forth regulatory T and B cells that suppress the immune system from overproducing harmful inflammatory responses triggered by herpes simplex virus infection. PSA reduced brainstem inflammation by promoting the appearance of IL-10 secreting regulatory T and B cells. IL-10 is a strong anti-inflammatory cytokine which creates a protective, anti-inflammatory response that prevents encephalitis.
The authors noted that they “assessed the immunomodulatory potential of PSA in HSE by infecting PSA or PBS treated 129S6 mice with HSV1, followed by delayed Acyclovir (ACV) treatment as often occurs in the clinical setting.” They found that mice pretreated with the candidate probiotic, B. fragilis or PSA, survived a lethal herpes simplex virus infection, whereas mice pretreated with a placebo did not survive despite the fact that both groups were given Acyclovir, an antiviral that is the standard of care for herpes simplex virus encephalitis. The surviving, PSA-treated mice, had dramatically reduced brainstem inflammation and altered cytokine and chemokine profiles. The finding suggests that the probiotic-derived PSA optimizes the immune system to fight against viruses, especially those that induce damaging inflammation.
The researchers reported on the important role B cells play in extinguishing inflammation. B cells are a type of white blood cell that secretes antibodies. When the scientists depleted mice of their B cells prior to PSA treatment, the mice lost their ability to marshal regulatory T cells and to secrete the anti-inflammatory cytokine IL-10. The researchers showed that B cells bound PSA, and this was crucial for the induction of protective regulatory T cells, which secrete the anti-inflammatory cytokine IL-10. Thus, eliminating B cells rendered the immune system weaponless in the fight against fatal herpes simplex virus brain inflammation. The data reveal the translational potential of PSA as an immunomodulatory symbiosis factor to orchestrate robust protective anti-inflammatory responses during viral infections.
“It’s possible that consumption of certain prebiotics, probiotics, or synbiotics may enhance your body’s natural ability to suppress inflammatory diseases,” noted Ramakrishna Chandran, PhD, assistant research professor in the department of molecular imaging & therapy and first author on the paper. “Our study provides an exciting proof of principle that needs further research validation, but it seems reasonable that what you decide to eat may affect your overall health and ability to fight off disease.”
“Although herpes simplex encephalitis is a rare brain inflammation disorder,” asserted Cantin, “the lessons we learned here might, with more research, be applicable to other viral infections such as other herpesviruses, influenza virus, West Nile virus, and maybe even viral respiratory diseases—conditions where inflammation begins to jeopardize the health of your body and brain function.”