Orally administered heat-killed Lactobacillus paracasei MCC1849 enhances antigen-specific IgA secretion and induces follicular helper T cells in mice.

Antigen-specific immunoglobulin (Ig) A plays a major role in host defense against infections in gut mucosal tissue. Follicular helper T (Tfh) cells are located in germinal centers and promote IgA production via interactions with germinal center B cells. Several studies have demonstrated that some lactic acid bacteria (LAB) strains activate the host's acquired immune system, inducing IgA secretion in the intestine. However, the precise molecular mechanisms underlying the effects of LAB on IgA production and Tfh cells are not fully resolved. Lactobacillus paracasei MCC1849 is a probiotic strain isolated from the intestine of a healthy adult. In this study, we investigated the effects of orally administered heat-killed MCC1849 on IgA production in the intestine and on Tfh cell induction in vivo. We found that orally administered MCC1849 induced antigen-specific IgA production in the small intestine, serum and lungs. We also observed that MCC1849 increased the proportion of IgA+ B cells and Tfh cells in Peyer's patches (PPs). In addition, MCC1849 increased the gene expression of IL-12p40, IL-10, IL-21, STAT4 and Bcl-6 associated with Tfh cell differentiation. These results suggest that orally administered MCC1849 enhances antigen-specific IgA production and likely affects Tfh cell differentiation in PPs.
Competing Interests: All the authors have read the manuscript and have approved this submission. The authors have the journal's policy and have the following conflicts: S. Arai, N. Iwabuchi, S. Takahashi, J-Z Xiao and F. Abe are employees of Morinaga Milk Industry Co., Ltd. The Morinaga Milk Industry Co., Ltd. is the commercial company that sells dairy products like milk, yoghurt, infant formula and so on. The Morinaga Milk Industry Co., Ltd. has filed patent applications on aspects of this work. S. Arai, N. Iwabuchi, and Dr. Hachimura are named as inventors on patent application number P2016-113378A (patent name: Increasing agent for follicular helper T cells). N. Iwabuchi, and J-Z Xiao are named as inventors with the Morinaga Milk Industry Co., Ltd. on patent application number WO2015/004949 A1 (patent name: Novel lactobacillus and novel lactobacillus-containing medicine, food, beverage and feed). These do not alter our adherence to all the PLOS ONE policies on sharing data and materials.