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J Immunol. 2016 Mar 1;196(5):2401-9. doi: 10.4049/jimmunol.1502470. Epub 2016 Jan 29.

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

Author information

1
Department of Pharmaceutics, University of Washington, Seattle, WA 98121; Washington National Primate Research Center, Seattle, WA 98121;
2
Genentech, South San Francisco, CA 94080;
3
Washington National Primate Research Center, Seattle, WA 98121;
4
Department of Pharmaceutics, University of Washington, Seattle, WA 98121;
5
AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory, Frederick, MD 21702;
6
Department of Microbiology, University of Washington, Seattle, WA 98195;
7
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115; and.
8
Division of Infectious Diseases and HIV Medicine, Drexel University, Philadelphia, PA 19104.
9
Department of Pharmaceutics, University of Washington, Seattle, WA 98121; Washington National Primate Research Center, Seattle, WA 98121; klattnr@uw.edu.

Abstract

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.

PMID:
26826246
PMCID:
PMC4761491
[Available on 2017-03-01]
DOI:
10.4049/jimmunol.1502470
[Indexed for MEDLINE]
Free PMC Article

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