Fungal sensing by dectin-1 directs the non-pathogenic polarization of TH17 cells through balanced type I IFN responses in human DCs

Sonja I. Gringhuis, Tanja M. Kaptein, Ester B. M. Remmerswaal, Agata Drewniak, Brigitte A. Wevers, Bart Theelen, Geert R. A. M. D’Haens, Teun Boekhout, Teunis B. H. Geijtenbeek

Research output: Contribution to journalArticleAcademicpeer-review

1 Citation (Scopus)


The non-pathogenic TH17 subset of helper T cells clears fungal infections, whereas pathogenic TH17 cells cause inflammation and tissue damage; however, the mechanisms controlling these distinct responses remain unclear. Here we found that fungi sensing by the C-type lectin dectin-1 in human dendritic cells (DCs) directed the polarization of non-pathogenic TH17 cells. Dectin-1 signaling triggered transient and intermediate expression of interferon (IFN)-β in DCs, which was mediated by the opposed activities of transcription factors IRF1 and IRF5. IFN-β-induced signaling led to integrin αvβ8 expression directly and to the release of the active form of the cytokine transforming growth factor (TGF)-β indirectly. Uncontrolled IFN-β responses as a result of IRF1 deficiency induced high expression of the IFN-stimulated gene BST2 in DCs and restrained TGF-β activation. Active TGF-β was required for polarization of non-pathogenic TH17 cells, whereas pathogenic TH17 cells developed in the absence of active TGF-β. Thus, dectin-1-mediated modulation of type I IFN responses allowed TGF-β activation and non-pathogenic TH17 cell development during fungal infections in humans.
Original languageEnglish
Pages (from-to)1735-1748
Number of pages14
JournalNature immunology
Issue number12
Early online date2022
Publication statusPublished - Dec 2022

Cite this