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Bacteroides fragilis polysaccharide A induces IL-10 secreting B and T cells that prevent viral encephalitis
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Journal Article
Bacteroides fragilis polysaccharide A induces IL-10 secreting B and T cells that prevent viral encephalitis
2019
Overview
The gut commensal
Bacteroides fragilis
or its capsular polysaccharide A (PSA) can prevent various peripheral and CNS sterile inflammatory disorders. Fatal herpes simplex encephalitis (HSE) results from immune pathology caused by uncontrolled invasion of the brainstem by inflammatory monocytes and neutrophils. Here we assess 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. Only PSA-treated mice survived, with dramatically reduced brainstem inflammation and altered cytokine and chemokine profiles. Importantly, PSA binding by B cells is essential for induction of regulatory CD4
+
and CD8
+
T cells secreting IL-10 to control innate inflammatory responses, consistent with the lack of PSA mediated protection in Rag
−/−
, B cell- and IL-10-deficient mice. Our data reveal the translational potential of PSA as an immunomodulatory symbiosis factor to orchestrate robust protective anti-inflammatory responses during viral infections.
The capsular polysaccharide A (PSA) of
Bacteroides fragilis
is known to have immunomodulatory capability during sterile inflammatory disorders. Here Ramakrishna and colleagues show that PSA administration in a murine model of herpes simplex encephalitis induces IL-10 producing B and T cell populations that confer protection against lethal challenge and brain pathology.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 13/1
/ 13/106
/ 13/21
/ 13/31
/ 64/60
/ 82/16
/ 82/83
/ 96/106
/ 96/34
/ Animals
/ Antiviral Agents - therapeutic use
/ Bacteroides fragilis - immunology
/ Bacteroides fragilis - metabolism
/ Encephalitis, Herpes Simplex - drug therapy
/ Encephalitis, Herpes Simplex - immunology
/ Encephalitis, Herpes Simplex - virology
/ Female
/ Gastrointestinal Microbiome - immunology
/ Herpesvirus 1, Human - immunology
/ Herpesvirus 1, Human - pathogenicity
/ Host Microbial Interactions - immunology
/ Humanities and Social Sciences
/ Humans
/ Male
/ Mice
/ Polysaccharides, Bacterial - immunology
/ Polysaccharides, Bacterial - metabolism
/ Science
