Plasmacytoid Dendritic Cells Mediate Anti-inflammatory Responses to a Gut Commensal Molecule via Both Innate and Adaptive Mechanisms

被引:236
作者
Dasgupta, Suryasarathi [1 ]
Erturk-Hasdemir, Deniz [1 ]
Ochoa-Reparaz, Javier [2 ]
Reinecker, Hans-Christian [3 ]
Kasper, Dennis L. [1 ]
机构
[1] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Div Immunol, Boston, MA 02115 USA
[2] Univ Calif Santa Barbara, Ctr Nanomed, Sanford Burnham Med Res Inst, Santa Barbara, CA 93106 USA
[3] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA
关键词
REGULATORY T-CELLS; INDUCIBLE COSTIMULATOR LIGAND; ORAL TOLERANCE; ZWITTERIONIC POLYSACCHARIDES; INDOLEAMINE 2,3-DIOXYGENASE; INTESTINAL INFLAMMATION; IMMUNE-RESPONSES; HUMAN MICROBIOTA; SIGLEC-H; INDUCTION;
D O I
10.1016/j.chom.2014.03.006
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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.
引用
收藏
页码:413 / 423
页数:11
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