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Published on: May 2, 2017
Enhancement of Microbiota in Healthy Macaques Results in Beneficial Modulation of Mucosal and Systemic Immune
Jennifer A Manuzak1, Tiffany Hensley-McBain1, Alexander S Zevin1
1Department of Pharmaceutics, University of Washington, Seattle, WA 98121; Washington National Primate Research Center, Seattle, WA 98121;
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.
Insights
Probiotic VSL#3 enhances mucosal immunity by increasing IgA-producing B cells and T follicular helper cells in macaques. This probiotic therapy may improve vaccine efficacy and mucosal protection against infection.
Area of Science:
- Immunology
- Microbiology
- Gastroenterology
Background:
- Mucosal surfaces are key sites for infection susceptibility.
- Probiotics (PBio) modulate gut microbiota to improve health.
- Understanding probiotic effects on mucosal immunity is crucial for vaccine development.
Purpose of the Study:
- To assess the longitudinal impact of daily VSL#3 probiotic treatment on cellular and humoral immunity and inflammation in healthy macaques.
- To elucidate the mechanisms by which probiotics enhance mucosal immune defenses.
Main Methods:
- Daily VSL#3 probiotic administration to healthy macaques.
- Analysis of immune cell populations (B cells, T follicular helper cells, APCs) in the colon and lymph nodes.
- Measurement of IgA expression and inflammatory markers.
- Assessment of HEK293 cell responses to Toll-like receptor (TLR) agonists.
Main Results:
- VSL#3 significantly increased IgA-expressing B cells in the colon and lymph nodes.
- Elevated T follicular helper cell frequencies and lymph node follicles were observed.
- Increased frequencies of IL-23(+) antigen-presenting cells (APCs) in the colon correlated with T follicular helper cells.
- VSL#3 downmodulated responses of TLR2, TLR3, TLR4, and TLR9-expressing cells to specific stimuli.
Conclusions:
- Probiotic VSL#3 enhances mucosal immune responses, including IgA production and T follicular helper cell activity.
- These findings suggest a mechanism for probiotic benefits on mucosal health.
- Probiotic therapy may be a valuable strategy to augment vaccine efficacy and enhance protection against mucosal infections.
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