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, Stanley Langevin, R. Keith Reeves, Elias K. Haddad, Nichole R. Klatt

Research output: Contribution to journalArticlepeer-review

45 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)2401-2409
Number of pages9
JournalJournal of Immunology
Issue number5
StatePublished - Mar 1 2016
Externally publishedYes

Bibliographical note

Funding Information:
We thank all veterinary staff of the Washington National Primate Research Center for animal studies; Michael Koday for assistance with tissue processing; Sigma-t for generous contribution of VSL#3 probiotics for these studies; Dr. Jason Brenchley for helpful advice in preparing this manuscript; and the Histology and Immunohistochemistry Core of the University of Washington, Department of Comparative Pathology, for assistance with tissue preparation.

Publisher Copyright:
©2016 by The American Association of Immunologists, Inc.


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