Recognition of fungal RNA by TLR 7 has a nonredundant role in host defense against experimental candidiasis

Abstract

Despite convincing evidence for involvement of members of the Toll‐like receptor (TLR) family in fungal recognition, little is known of the functional role of individual TLR s in antifungal defenses. We found here that TLR 7 was partially required for the induction of IL‐12 (IL‐12p70) by C andida albicans or S accharomyces cerevisiae. Moreover, the IL‐12p70 response was completely abrogated in cells from 3d mice, which are unable to mob‐ilize TLR s to endosomal compartments, as well as in cells from mice lacking either the TLR adaptor M y D 88 or the IRF 1 transcription factor. Notably, purified fungal RNA recapitulated IL‐12p70 induction by whole yeast. Although RNA could also induce moderate TLR 7‐dependent IL‐23 and tumor necrosis factor‐alpha (TNF‐α) secretion, TLR 7 and other endosomal TLR s were redundant for IL‐23 or TNF‐α induction by whole fungi. Importantly, mice lacking TLR 7 or IRF 1 were hypersusceptible to systemic C. albicans infection. Our data suggest that IRF 1 is downstream of a novel, nonredundant fungal recognition pathway that has RNA as a major target and requires phagosomal recruitment of intracellular TLR s. This pathway differs from those involved in IL‐23 or TNF‐α responses, which we show here to be independent from translocation of intracellular TLR s, phagocytosis, or phagosomal acidification.