title: Bacterial signalling overrides cytokine signalling and modifies dendritic cell differentiation.
abstract: Heterogeneity of dendritic cells (DC) is evident in the gut-associated lymphoid tissue and determined, in part, by incompletely understood local environmental factors. Bacterial signalling is likely to be a dominant influence on precursor cells when recruited to the mucosa. We assessed the influence of commensal bacteria on DC differentiation and function. Murine bone marrow progenitors were exposed to Lactobacillus salivarius, Bifidobacterium breve or Bifidobacterium infantis. Differences in cell surface phenotype and function were assessed. Myeloid differentiation factor 88(-/-) (MyD88) cells were used to determine the influence of Toll-like receptor signalling. While bacterial strains varied in impact, there was a consistent dose-dependent inhibition of DC differentiation with a shift toward a Gr-1(+) CD11b(+) monocyte-like phenotype. A single bacterium on a per cell basis (1 : 1) was sufficient to alter cell phenotype. The effect was only evident in early precursors. Enhanced interleukin-10 production correlated with increased Forkhead box P3 expression and reduced T-cell proliferation. The bacterial effect on DC differentiation was found to be MyD88-dependent. Signalling by enteric commensals through pattern recognition receptors on precursor cells alters DC differentiation and results in cells that are phenotypically monocyte-like and functionally suppressive. This may account for some of the features of mucosal immune tolerance to the microbiota.
authors.affiliation: Alimentary Pharmabiotic Centre, University College Cork, National University of Ireland, Cork, Ireland.
authors.forename: Julie M
authors.initials: JM
authors.lastname: Davies
authors.forename: Barbara
authors.initials: B
authors.lastname: Sheil
authors.forename: Fergus
authors.initials: F
authors.lastname: Shanahan
mesh_terms: D000818:Animals; D001644:Bifidobacterium / Q000276:immunology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology*; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000276:immunology / Q000382:microbiology*; D007108:Immune Tolerance; D018928:Immunity, Mucosal; D007422:Intestines / Q000276:immunology* / Q000382:microbiology; D007778:Lactobacillus / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000378:metabolism; D010587:Phagocytosis / Q000276:immunology; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology / Q000382:microbiology; D015854:Up-Regulation / Q000276:immunology
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D053594:Myeloid Differentiation Factor 88