With more than thirty million HIV-infected individuals worldwide, developing an effective vaccine to prevent new HIV infections remains a top priority in contemporary biomedical research. Given the critical role of mucosal surfaces in susceptibility to HIV, it is imperative that we induce effective mucosal responses. However, current approaches to enhance mucosal immunity have not been successful in preventing HIV acquisition. Modulating the microbiota in the GI tract 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 (PBio) on cellular and humoral immunity and inflammation in healthy macaques.
Five macaques (SIV-) were treated with the PBio VSL#3. Colon, jejunum and LN were sampled prior to PBio treatment (PBio-tx) and at days 28 and 77/80 post-treatment. Indicators of cellular and humoral immunity and inflammation were assessed using multi-parameter flow cytometry.
PBio-tx resulted in significantly increased frequencies of B cells expressing IgA in the colon (p=0.0072) and LN (p=0.0151) d80 post-PBio-tx, likely due to persistently increased LN T follicular helper cell (Tfh) frequencies (d28: p=0.0085; d80: p=0.0173). Increased frequencies of IL-23+ antigen presenting cells (APCs) in the colon (p=0.0173) and LN (p=0.0475) were found d28 post-PBio-tx, and colon IL-23+ APCs correlated with the frequency of LN Tfh (p=0.0358, r=0.5446). Increased frequencies of ILC3 in the jejunum were observed (p=0.005) d80 post-PBio-tx. The frequencies of activated (HLA-DR+) and proliferating (Ki-67+) CD4+ T cells were significantly decreased in the colon at d28 (p=0.0310 and 0.0042, respectively) and d80 (p=0.0612 and 0.0013, respectively) post-pBio-tx. Finally, VSL#3 significantly down-modulated the response of TLR2-, 3-, 4-, and 9-expressing HEK293 cells to stimulation with Pam3CSK4, Poly(I:C), LPS, and ODN2006, respectively (p<0.0001).
These data provide a mechanism for the beneficial impact of PBio on mucosal health and has potential implications for using PBio-tx to alter mucosal immunity in the context of vaccination or preventative approaches. In particular, the immunomodulatory properties of PBio-tx in conjunction with HIV vaccination may provide an opportunity for enhanced mucosal HIV vaccine responses that could improve protection from infection by improving immune defenses at the mucosal portal of entry and regulating the frequency of potential target cells.