title: 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.
authors.affiliation: Otsu Nutraceuticals Research Institute, Otsuka Pharmaceutical Co., Ltd., Shiga, Japan; Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan; Laboratory of Vaccine Materials, National Institute of Biomedical Innovation, Osaka, Japan.
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Kotani
authors.affiliation: Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan; International Research and Development Center for Mucosal Vaccines, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan; Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency, Tokyo, Japan; Laboratory of Vaccine Materials, National Institute of Biomedical Innovation, Osaka, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Kunisawa
authors.affiliation: Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Suzuki
authors.affiliation: Otsu Nutraceuticals Research Institute, Otsuka Pharmaceutical Co., Ltd., Shiga, Japan.
authors.forename: Ikutaro
authors.initials: I
authors.lastname: Sato
authors.affiliation: Otsu Nutraceuticals Research Institute, Otsuka Pharmaceutical Co., Ltd., Shiga, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Saito
authors.affiliation: Otsu Nutraceuticals Research Institute, Otsuka Pharmaceutical Co., Ltd., Shiga, Japan.
authors.forename: Masamichi
authors.initials: M
authors.lastname: Toba
authors.affiliation: Otsu Nutraceuticals Research Institute, Otsuka Pharmaceutical Co., Ltd., Shiga, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Kohda
authors.affiliation: Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan; International Research and Development Center for Mucosal Vaccines, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan; Department of Medical Genome Science, Graduate School of Frontier Science, The University of Tokyo, Chiba, Japan; Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kiyono
mesh_terms: D000818:Animals; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology*; D007070:Immunoglobulin A / Q000096:biosynthesis*; D015850:Interleukin-6 / Q000096:biosynthesis; D007778:Lactobacillus / Q000502:physiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010581:Peyer's Patches / Q000276:immunology* / Q000382:microbiology; D051195:Toll-Like Receptor 2 / Q000378:metabolism*
chemical_list: D007070:Immunoglobulin A; D015850:Interleukin-6; D051195:Toll-Like Receptor 2