Lack of toll IL-1R8 exacerbates Th17 cell responses in fungal infection

Silvia Bozza, Teresa Zelante, Silvia Moretti, Pierluigi Bonifazi, Antonella DeLuca, Carmen D'Angelo, Gloria Giovannini, Cecilia Garlanda, Louis Boon, Francesco Bistoni, Paolo Puccetti, Alberto Mantovani, Luigina Romani

Research output: Contribution to journalArticlepeer-review

Abstract

TLRs contribute to the inflammatory response in fungal infections. Although inflammation is an essential component of the protective response to fungi, its dysregulation may significantly worsen fungal diseases. In this study, we tested the hypothesis that Toll IL-1R8 (TIR8)/single Ig IL-1-related receptor, a member of the IL-1R family acting as a negative regulator of TLR/IL-1R signaling, affects TLR responses in fungal infections. Genetically engineered Tir8-/- mice were assessed for inflammatory and adaptive Th cell responses to Candida albicans and Aspergillus fumigatus. Inflammatory pathology and susceptibility to infection were higher in Tir8-/- mice and were causally linked to the activation of the Th17 pathway. IL-1R signaling was involved in Th17 cell activation by IL-6 and TGF-β in that limited inflammatory pathology and relative absence of Th17 cell activation were observed in IL-1RI-/- mice. These data demonstrate that TIR8 is required for host resistance to fungal infections and that it functions to negatively regulate IL-1-dependent activation of inflammatory Th17 responses. TIR8 may contribute toward fine-tuning the balance between protective immunity and immunopathology in infection.

Original languageEnglish
Pages (from-to)4022-4031
Number of pages10
JournalJournal of Immunology
Volume180
Issue number6
Publication statusPublished - Mar 15 2008

ASJC Scopus subject areas

  • Immunology

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