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Bacteroides fragilis polysaccharide A induces IL-10 secreting B and T cells that prevent viral encephalitis

Author

Listed:
  • Chandran Ramakrishna

    (Beckman Research Institute of City of Hope)

  • Maciej Kujawski

    (Beckman Research Institute of City of Hope)

  • Hiutung Chu

    (California Institute of Technology)

  • Lin Li

    (Beckman Research Institute of City of Hope)

  • Sarkis K. Mazmanian

    (California Institute of Technology)

  • Edouard M. Cantin

    (Beckman Research Institute of City of Hope)

Abstract

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.

Suggested Citation

  • Chandran Ramakrishna & Maciej Kujawski & Hiutung Chu & Lin Li & Sarkis K. Mazmanian & Edouard M. Cantin, 2019. "Bacteroides fragilis polysaccharide A induces IL-10 secreting B and T cells that prevent viral encephalitis," Nature Communications, Nature, vol. 10(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-09884-6
    DOI: 10.1038/s41467-019-09884-6
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    Cited by:

    1. Rabindra K. Mandal & Anita Mandal & Joshua E. Denny & Ruth Namazii & Chandy C. John & Nathan W. Schmidt, 2023. "Gut Bacteroides act in a microbial consortium to cause susceptibility to severe malaria," Nature Communications, Nature, vol. 14(1), pages 1-18, December.

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