Date Published: June 13, 2018
Publisher: Public Library of Science
Author(s): Satoshi Arai, Noriyuki Iwabuchi, Sachiko Takahashi, Jin-zhong Xiao, Fumiaki Abe, Satoshi Hachimura, Hossam M. Ashour.
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.
Host immune system responses against infections can be divided into two classes, innate and acquired responses. Immunoglobulin (Ig) A plays a major role in the mucosal defense of the host against infections as a part of acquired immunity. The primary role of mucosal IgA has been reported to be the neutralization of harmful bacteria and viruses by interfering with their motility or by inhibiting their adherence to epithelial cells . Gut-associated lymphoid tissues (GALTs), such as Peyer’s patches (PPs), are important inductive sites for the initiation and generation of IgA-committed B cells . Several studies have revealed that dendritic cells (DCs) in PPs induce IgA class-switch recombination (CSR) through a T cell-independent pathway by producing retinoic acid (RA), a proliferation-inducing ligand (APRIL) and B-cell activating factor (BAFF) . DCs may also enhance the development and/or secretion of IgA-producing cells . In addition, antigen-specific helper T cells are primed and activated by DCs to support the IgA CSR of IgM+ B cells to IgA+ B cells through the secretion of transforming growth factor-β (TGF-β), interleukin-4 (IL-4) and the CD40 ligand . Antigen-specific IgA production and IgA+ B cell development in PPs are regulated by follicular helper T (Tfh) cells . Tfh cells have recently been proposed to be another distinct subset of helper T cells that play roles in enhancing germinal center formation and regulating germinal center B cell differentiation . Tfh cells are characterized by the selective expression of a variety of molecules, including the surface markers CXC chemokine receptor 5 (CXCR5), programmed death 1 (PD-1), and inducible co-stimulator (ICOS), and the production of the cytokine IL-21 . IL-6 and IL-21 act via STAT3 and have been proposed to be drivers of Tfh cell differentiation .
LAB species have been reported to modulate host immune responses , and there are many reports that some probiotic LAB induce IL-12 production, affecting intestinal DCs and enhancing host innate immunity . We have previously reported that heat-killed MCC1849 affects host acquired immunity and increases the antibody response against IFV vaccination in elderly over 85 years old . The capacity of MCC1849 for IL-12 induction is considerably greater than that of other Lactobacillus type strains (Fig 1A). In the present study, we showed that the administration of MCC1849 induced antigen-specific IgA production and increased the proportion of Tfh cells in PPs (Figs 2–5).