Role of Lactobacillus pentosus Strain b240 and the Toll-like receptor 2 axis in Peyer's patch dendritic cell-mediated immunoglobulin A enhancement.

Abstract

Lactic acid bacteria are well known to possess immune-modulating effects, but the mechanisms underlying their modulation of the gut immune system are not fully understood. Here, we examined the localization of heat-killed Lactobacillus pentosus strain b240 (b240) in intestinal tissues and the effect of b240 on adaptive immune cascades in the gut. Histological analysis showed that b240 co-localized with dendritic cells (DCs) in the subepithelial dome region of Peyer's patches (PPs). In a PP cell culture system, b240 promoted the production of immunoglobulin A (IgA), interleukin (IL)-6, IL-10, interferon (IFN)-γ, and tumor necrosis factor, but not IL-4, IL-5, B-cell activating factors, IFN-α, IFN-β, and transforming growth factor-β1. The enhanced IgA production by b240 was attenuated by neutralizing IL-6, a potent IgA-enhancing cytokine. b240 stimulated DCs to produce an elevated amount of IL-6 in a Toll-like receptor (TLR) 2-, but not TLR4- or TLR9-dependent manner. Finally, we demonstrated that TLR2-mediated IL-6 production from PP DCs in response to b240 activated B cells to produce a large amount of IgA in a DC-B cell co-culture system. Our findings open up the possibility that the heat-killed form of Lactobacillus pentosus strain b240 can be used as a TLR2-mediated DC-activating biologic for enhancing IgA production in the intestine.