TY - JOUR
T1 - Plasmacytoid dendritic cells mediate anti-inflammatory responses to a gut commensal molecule via both innate and adaptive mechanisms
AU - Dasgupta, Suryasarathi
AU - Erturk-Hasdemir, Deniz
AU - Ochoa-Reparaz, Javier
AU - Reinecker, Hans Christian
AU - Kasper, Dennis L.
N1 - Funding Information:
This work was supported by a Senior Research Award from the Crohn’s and Colitis Foundation of America and R21 NIAID (AI1090102) to D.L.K. We thank B. Reinap, R.T. Bronson, and J. McCoy for PSA purification, histopathology discussions, and editorial expertise, respectively; N. Reading, H. Chun, E. Troy, and N. Surana for technical help; and Diane Mathis (Harvard Medical School) for manuscript review and helpful suggestions.
PY - 2014/4/9
Y1 - 2014/4/9
N2 - 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.
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.
UR - http://www.scopus.com/inward/record.url?scp=84898647980&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84898647980&partnerID=8YFLogxK
U2 - 10.1016/j.chom.2014.03.006
DO - 10.1016/j.chom.2014.03.006
M3 - Article
C2 - 24721570
AN - SCOPUS:84898647980
SN - 1931-3128
VL - 15
SP - 413
EP - 423
JO - Cell Host and Microbe
JF - Cell Host and Microbe
IS - 4
ER -