Plasmacytoid dendritic cells mediate anti-inflammatory responses to a gut commensal molecule via both innate and adaptive mechanisms.
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.
Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA.
Suryasarathi
S
Dasgupta
Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA.
Deniz
D
Erturk-Hasdemir
Center for Nanomedicine, Sanford-Burnham Medical Research Institute at the University of California, Santa Barbara, CA 93106-9625, USA.
Javier
J
Ochoa-Reparaz
Division of Gastroenterology, Massachusetts General Hospital, Boston, MA 02114, USA.
Hans-Christian
HC
Reinecker
Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: dennis_kasper@hms.harvard.edu.
Dennis L
DL
Kasper
D056704:Adaptive Immunity; D019264:Adoptive Transfer; D000818:Animals; D018122:B7-1 Antigen / Q000235:genetics; D051940:B7-2 Antigen / Q000235:genetics; D001441:Bacteroides fragilis / Q000276:immunology*; D001854:Bone Marrow Cells / Q000276:immunology; D018106:CD28 Antigens / Q000235:genetics; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000637:transplantation; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D005260:Female; D041981:Gastrointestinal Tract / Q000276:immunology* / Q000382:microbiology; D007113:Immunity, Innate; D060945:Inducible T-Cell Co-Stimulator Ligand / Q000235:genetics; D007249:Inflammation / Q000276:immunology; D016753:Interleukin-10 / Q000378:metabolism; D008212:Lymphocyte Depletion; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D023421:Models, Animal; D011135:Polysaccharides, Bacterial / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000096:biosynthesis / Q000378:metabolism
D018122:B7-1 Antigen; D051940:B7-2 Antigen; D018106:CD28 Antigens; C497965:Cd86 protein, mouse; C556062:IL10 protein, mouse; C400230:Icosl protein, mouse; D060945:Inducible T-Cell Co-Stimulator Ligand; D011135:Polysaccharides, Bacterial; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D016753:Interleukin-10