TY - JOUR
T1 - Toll-Like Receptor 2 Suppresses Immunity against Candida albicans through Induction of IL-10 and Regulatory T Cells
AU - Netea, Mihai G.
AU - Sutmuller, Roger
AU - Hermann, Corinna
AU - Van Der Graaf, Chantal A.A.
AU - Van Der Meer, Jos W.M.
AU - Van Krieken, Johan H.
AU - Hartung, Thomas
AU - Adema, Gosse
AU - Kullberg, Bart Jan
PY - 2004/3/15
Y1 - 2004/3/15
N2 - Toll-like receptor (TLR) 2 and TLR4 play a pivotal role in recognition of Candida albicans. We demonstrate that TLR2-/- mice are more resistant to disseminated Candida infection, and this is associated with increased chemotaxis and enhanced candidacidal capacity of TLR2-/- macrophages. Although production of the proinflammatory cytokines TNF, IL-1α, and IL-1β is normal, IL-10 release is severely impaired in the TLR2-/- mice. This is accompanied by a 50% decrease in the CD4+CD25+ regulatory T (Treg) cell population in TLR2 -/- mice. In vitro studies confirmed that enhanced survival of Treg cells was induced by TLR2 agonists. The deleterious role of Treg cells on the innate immune response during disseminated candidiasis was underscored by the improved resistance to this infection after depletion of Treg cells. In conclusion, C. albicans induces immunosuppression through TLR2-derived signals that mediate increased IL-10 production and survival of Treg cells. This represents a novel mechanism in the pathogenesis of fungal infections.
AB - Toll-like receptor (TLR) 2 and TLR4 play a pivotal role in recognition of Candida albicans. We demonstrate that TLR2-/- mice are more resistant to disseminated Candida infection, and this is associated with increased chemotaxis and enhanced candidacidal capacity of TLR2-/- macrophages. Although production of the proinflammatory cytokines TNF, IL-1α, and IL-1β is normal, IL-10 release is severely impaired in the TLR2-/- mice. This is accompanied by a 50% decrease in the CD4+CD25+ regulatory T (Treg) cell population in TLR2 -/- mice. In vitro studies confirmed that enhanced survival of Treg cells was induced by TLR2 agonists. The deleterious role of Treg cells on the innate immune response during disseminated candidiasis was underscored by the improved resistance to this infection after depletion of Treg cells. In conclusion, C. albicans induces immunosuppression through TLR2-derived signals that mediate increased IL-10 production and survival of Treg cells. This represents a novel mechanism in the pathogenesis of fungal infections.
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U2 - 10.4049/jimmunol.172.6.3712
DO - 10.4049/jimmunol.172.6.3712
M3 - Article
C2 - 15004175
AN - SCOPUS:1542409922
SN - 0022-1767
VL - 172
SP - 3712
EP - 3718
JO - Journal of Immunology
JF - Journal of Immunology
IS - 6
ER -