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- Title
Recognition of fungal RNA by TLR7 has a nonredundant role in host defense against experimental candidiasis.
- Authors
Biondo, Carmelo; Malara, Antonio; Costa, Alessandro; Signorino, Giacomo; Cardile, Francesco; Midiri, Angelina; Galbo, Roberta; Papasergi, Salvatore; Domina, Maria; Pugliese, Michela; Teti, Giuseppe; Mancuso, Giuseppe; Beninati, Concetta
- 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 TLRs in antifungal defenses. We found here that TLR7 was partially required for the induction of IL-12 ( IL-12p70) by Candida albicans or Saccharomyces cerevisiae. Moreover, the IL-12p70 response was completely abrogated in cells from 3d mice, which are unable to mob-ilize TLRs to endosomal compartments, as well as in cells from mice lacking either the TLR adaptor My D88 or the IRF1 transcription factor. Notably, purified fungal RNA recapitulated IL-12p70 induction by whole yeast. Although RNA could also induce moderate TLR7-dependent IL-23 and tumor necrosis factor-alpha ( TNF-α) secretion, TLR7 and other endosomal TLRs were redundant for IL-23 or TNF-α induction by whole fungi. Importantly, mice lacking TLR7 or IRF1 were hypersusceptible to systemic C. albicans infection. Our data suggest that IRF1 is downstream of a novel, nonredundant fungal recognition pathway that has RNA as a major target and requires phagosomal recruitment of intracellular TLRs. This pathway differs from those involved in IL-23 or TNF-α responses, which we show here to be independent from translocation of intracellular TLRs, phagocytosis, or phagosomal acidification.
- Publication
European Journal of Immunology, 2012, Vol 42, Issue 10, p2632
- ISSN
0014-2980
- Publication type
Article
- DOI
10.1002/eji.201242532