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.
Highlights
Gut mucosal epithelial surfaces are in continuous contact with a heterogeneous population of endogenous microbiota and are exposed to foods, exotic microbes, and viruses [1,2]
Our results suggest that orally administered b240 was taken up by the subepithelial dome (SED) region of Peyer’s patches (PPs) and induced b240-Toll-like receptor (TLR) 2 axis-mediated the production of the proinflammatory cytokine IL-6 from PP dendritic cells (DCs) to activate B cells to produce a large amount of immunoglobulin A (IgA)
To examine whether these cytokines are involved in enhanced IgA production, PP cells were cultured with b240 in the presence of blocking antibodies specific for IL-6, IFN-c, or tumor necrosis factor (TNF)
Summary
Gut mucosal epithelial surfaces are in continuous contact with a heterogeneous population of endogenous microbiota and are exposed to foods, exotic microbes, and viruses [1,2]. One of unique features of the intestinal immune system is a highly specialized antibody inclination towards immunoglobulin A (IgA) production. The secretory form of IgA (SIgA) antibodies has been shown to play critical roles in both the protective and symbiotic phases of intestinal immunity. For the production of SIgA, gut-associated lymphoid tissues (GALT) such as Peyer’s patches (PPs) are an important inductive site for the initiation and generation of antigen (Ag)-specific IgAcommitted B cells [5]. Several studies revealed that PP DCs induce IgA CSR via a T cell-independent pathway by producing retinoic acid (RA) [23] or a proliferation-inducing ligand (APRIL) and B-cell activating factor (BAFF) [24,25]
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