TY - JOUR T1 - Plasmacytoid dendritic cells mediate anti-inflammatory responses to a gut commensal molecule via both innate and adaptive mechanisms JF - Cell Host Microbe Y1 - 2014 A1 - Dasgupta, Suryasarathi A1 - Erturk-Hasdemir, Deniz A1 - Ochoa-Reparaz, Javier A1 - Reinecker, Hans-Christian A1 - Kasper, Dennis L KW - Adaptive Immunity KW - Adoptive Transfer KW - Animals KW - B7-1 Antigen KW - B7-2 Antigen KW - Bacteroides fragilis KW - Bone Marrow Cells KW - CD28 Antigens KW - CD4-Positive T-Lymphocytes KW - Cells, Cultured KW - Dendritic Cells KW - Encephalomyelitis, Autoimmune, Experimental KW - Female KW - Gastrointestinal Tract KW - Immunity, Innate KW - Inducible T-Cell Co-Stimulator Ligand KW - Inflammation KW - Interleukin-10 KW - Lymphocyte Depletion KW - Mice KW - Mice, Inbred C57BL KW - Mice, Knockout KW - Models, Animal KW - Polysaccharides, Bacterial KW - Toll-Like Receptor 2 AB - Polysaccharide A (PSA), the archetypical immunomodulatory molecule of the gut commensal Bacteroides fragilis, induces regulatory T cells to secrete the anti-inflammatory cytokine interleukin-10 (IL-10). The cellular mediators of PSA's immunomodulatory properties are incompletely understood. In a mouse model of colitis, we find that PSA requires both innate and adaptive immune mechanisms to generate protection. Plasmacytoid DCs (PDCs) exposed to PSA do not produce proinflammatory cytokines, but instead they specifically stimulate IL-10 secretion by CD4+ T cells and efficiently mediate PSA-afforded immunoprotection. PSA induces and preferentially ligates Toll-like receptor 2 on PDCs but not on conventional DCs. Compared with other TLR2 ligands, PSA is better at enhancing PDC expression of costimulatory molecules required for protection against colitis. PDCs can thus orchestrate the beneficial immunoregulatory interaction of commensal microbial molecules, such as PSA, through both innate and adaptive immune mechanisms. VL - 15 IS - 4 U1 - http://www.ncbi.nlm.nih.gov/pubmed/24721570?dopt=Abstract ER -