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Bacteroides fragilis polysaccharide A induces IL-10 secreting B and T cells that prevent viral encephalitis
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 ne...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6517419/ https://www.ncbi.nlm.nih.gov/pubmed/31089128 http://dx.doi.org/10.1038/s41467-019-09884-6 |
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author | Ramakrishna, Chandran Kujawski, Maciej Chu, Hiutung Li, Lin Mazmanian, Sarkis K. Cantin, Edouard M. |
author_facet | Ramakrishna, Chandran Kujawski, Maciej Chu, Hiutung Li, Lin Mazmanian, Sarkis K. Cantin, Edouard M. |
author_sort | Ramakrishna, Chandran |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6517419 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-65174192019-05-16 Bacteroides fragilis polysaccharide A induces IL-10 secreting B and T cells that prevent viral encephalitis Ramakrishna, Chandran Kujawski, Maciej Chu, Hiutung Li, Lin Mazmanian, Sarkis K. Cantin, Edouard M. Nat Commun Article 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. Nature Publishing Group UK 2019-05-14 /pmc/articles/PMC6517419/ /pubmed/31089128 http://dx.doi.org/10.1038/s41467-019-09884-6 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Ramakrishna, Chandran Kujawski, Maciej Chu, Hiutung Li, Lin Mazmanian, Sarkis K. Cantin, Edouard M. Bacteroides fragilis polysaccharide A induces IL-10 secreting B and T cells that prevent viral encephalitis |
title | Bacteroides fragilis polysaccharide A induces IL-10 secreting B and T cells that prevent viral encephalitis |
title_full | Bacteroides fragilis polysaccharide A induces IL-10 secreting B and T cells that prevent viral encephalitis |
title_fullStr | Bacteroides fragilis polysaccharide A induces IL-10 secreting B and T cells that prevent viral encephalitis |
title_full_unstemmed | Bacteroides fragilis polysaccharide A induces IL-10 secreting B and T cells that prevent viral encephalitis |
title_short | Bacteroides fragilis polysaccharide A induces IL-10 secreting B and T cells that prevent viral encephalitis |
title_sort | bacteroides fragilis polysaccharide a induces il-10 secreting b and t cells that prevent viral encephalitis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6517419/ https://www.ncbi.nlm.nih.gov/pubmed/31089128 http://dx.doi.org/10.1038/s41467-019-09884-6 |
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