Toll-Like Receptor 2 Suppresses Immunity against Candida albicans through Induction of IL-10 and Regulatory T Cells

Mihai G. Netea, Roger Sutmuller, Corinna Hermann, Chantal A.A. Van Der Graaf, Jos W.M. Van Der Meer, Johan H. Van Krieken, Thomas Hartung, Gosse Adema, Bart Jan Kullberg

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)3712-3718
Number of pages7
JournalJournal of Immunology
Volume172
Issue number6
DOIs
StatePublished - Mar 15 2004
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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