title: Secretory IgA in complex with Lactobacillus rhamnosus potentiates mucosal dendritic cell-mediated Treg cell differentiation via TLR regulatory proteins, RALDH2 and secretion of IL-10 and TGF-β.
abstract: The importance of secretory IgA in controlling the microbiota is well known, yet how the antibody affects the perception of the commensals by the local immune system is still poorly defined. We have previously shown that the transport of secretory IgA in complex with bacteria across intestinal microfold cells results in an association with dendritic cells in Peyer's patches. However, the consequences of such an interaction on dendritic cell conditioning have not been elucidated. In this study, we analyzed the impact of the commensal Lactobacillus rhamnosus, alone or associated with secretory IgA, on the responsiveness of dendritic cells freshly recovered from mouse Peyer's patches, mesenteric lymph nodes, and spleen. Lactobacillus rhamnosus-conditioned mucosal dendritic cells are characterized by increased expression of Toll-like receptor regulatory proteins [including single immunoglobulin interleukin-1 receptor-related molecule, suppressor of cytokine signaling 1, and Toll-interacting molecule] and retinaldehyde dehydrogenase 2, low surface expression of co-stimulatory markers, high anti- versus pro-inflammatory cytokine production ratios, and induction of T regulatory cells with suppressive function. Association with secretory IgA enhanced the anti-inflammatory/regulatory Lactobacillus rhamnosus-induced conditioning of mucosal dendritic cells, particularly in Peyer's patches. At the systemic level, activation of splenic dendritic cells exposed to Lactobacillus rhamnosus was partially dampened upon association with secretory IgA. These data suggest that secretory IgA, through coating of commensal bacteria, contributes to the conditioning of mucosal dendritic cells toward tolerogenic profiles essential for the maintenance of intestinal homeostasis.
authors.affiliation: R&D Laboratory, Division of Immunology and Allergy, CHUV, Centre des Laboratoires d'Epalinges, 1066 Epalinges, Switzerland.
authors.forename: Josip
authors.initials: J
authors.lastname: Mikulic
authors.affiliation: R&D Laboratory, Division of Immunology and Allergy, CHUV, Centre des Laboratoires d'Epalinges, 1066 Epalinges, Switzerland.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Longet
authors.affiliation: Nutrition and Health, Nestlé Research Center, 1000 Lausanne 26, Switzerland.
authors.forename: Laurent
authors.initials: L
authors.lastname: Favre
authors.affiliation: Nutrition and Health, Nestlé Research Center, 1000 Lausanne 26, Switzerland.
authors.forename: Jalil
authors.initials: J
authors.lastname: Benyacoub
authors.affiliation: R&D Laboratory, Division of Immunology and Allergy, CHUV, Centre des Laboratoires d'Epalinges, 1066 Epalinges, Switzerland.
authors.forename: Blaise
authors.initials: B
authors.lastname: Corthesy
mesh_terms: D000080924:Aldehyde Dehydrogenase 1 Family; D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000382:microbiology; D005260:Female; D007108:Immune Tolerance; D007071:Immunoglobulin A, Secretory / Q000378:metabolism*; D016753:Interleukin-10 / Q000378:metabolism; D052201:Lacticaseibacillus rhamnosus / Q000502:physiology*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009092:Mucous Membrane / Q000276:immunology*; D050697:Retinal Dehydrogenase / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D051193:Toll-Like Receptors / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D007071:Immunoglobulin A, Secretory; D051193:Toll-Like Receptors; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D000080924:Aldehyde Dehydrogenase 1 Family; C545372:ALDH1A2 protein, human; D050697:Retinal Dehydrogenase