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Enhancement of Microbiota in Healthy Macaques Results in Beneficial Modulation of Mucosal and Systemic Immune Function
Journal article   Open access   Peer reviewed

Enhancement of Microbiota in Healthy Macaques Results in Beneficial Modulation of Mucosal and Systemic Immune Function

Jennifer A Manuzak, Tiffany Hensley-McBain, Alexander S Zevin, Charlene Miller, Rafael Cubas, Brian Agricola, Jill Gile, Laura Richert-Spuhler, Gabriela Patilea, Jacob D Estes, …
The Journal of immunology (1950), v 196(5), pp 2401-2409
01 Mar 2016
PMID: 26826246
url
https://www.jimmunol.org/content/jimmunol/196/5/2401.full.pdfView
Published, Version of Record (VoR) Open
url
https://doi.org/10.4049/jimmunol.1502470View
Published, Version of Record (VoR) Open

Abstract

Animals Antigen-Presenting Cells B-Lymphocytes - immunology B-Lymphocytes - metabolism Cell Line Colon - immunology Colon - microbiology Gastrointestinal Microbiome - immunology Humans Immunity Immunity, Innate Immunity, Mucosal Immunoglobulin A - immunology Immunoglobulin G - immunology Interleukin-23 - biosynthesis Lymph Nodes - immunology Lymph Nodes - metabolism Lymphocyte Activation - immunology Macaca Microbiota Mucous Membrane - immunology Mucous Membrane - microbiology Probiotics - administration & dosage Signal Transduction T-Lymphocytes, Helper-Inducer - immunology T-Lymphocytes, Helper-Inducer - metabolism Toll-Like Receptors - metabolism
Given the critical role of mucosal surfaces in susceptibility to infection, it is imperative that effective mucosal responses are induced when developing efficacious vaccines and prevention strategies for infection. Modulating the microbiota in the gastrointestinal (GI) tract through the use of probiotics (PBio) is a safe and well-tolerated approach to enhance mucosal and overall health. We assessed the longitudinal impact of daily treatment with the VSL#3 probiotic on cellular and humoral immunity and inflammation in healthy macaques. PBio therapy resulted in significantly increased frequencies of B cells expressing IgA in the colon and lymph node (LN), likely because of significantly increased LN T follicular helper cell frequencies and LN follicles. Increased frequencies of IL-23(+) APCs in the colon were found post-PBio treatment, which correlated with LN T follicular helper cells. Finally, VSL#3 significantly downmodulated the response of TLR2-, TLR3-, TLR4-, and TLR9-expressing HEK293 cells to stimulation with Pam3CSK4, polyinosinic-polycytidylic acid, LPS, and ODN2006, respectively. These data provide a mechanism for the beneficial impact of PBio on mucosal health and implicates the use of PBio therapy in the context of vaccination or preventative approaches to enhance protection from mucosal infection by improving immune defenses at the mucosal portal of entry.

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Collaboration types
Industry collaboration
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Web of Science research areas
Immunology
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