Selective C-Rel Activation via Malt1 Controls Anti-Fungal TH-17 Immunity by Dectin-1 and Dectin-2

PLoS Pathogens

Bart Theelen¹  Teun Boekhout¹  Teunis B. H. Geijtenbeek²  Tanja M. Kaptein²  Sonja I. Gringhuis²  Brigitte A. Wevers²  Toni M. M. van Capel³  Esther C. de Jong³ 

[1] CBS-KNAW Fungal Biodiversity Centre, Utrecht, The Netherlands;Center of Infection and Immunity Amsterdam and Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands;Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

关键词: Cytokines;    C;    ida albicans;    Transcription factors;    C;    ida;    Fungal pathogens;    Immune response;    Fungi;    Cell-mediated immunity;   

DOI  :  10.1371/journal.ppat.1001259

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

C-type lectins dectin-1 and dectin-2 on dendritic cells elicit protective immunity against fungal infections through induction of TH1 and TH-17 cellular responses. Fungal recognition by dectin-1 on human dendritic cells engages the CARD9-Bcl10-Malt1 module to activate NF-κB. Here we demonstrate that Malt1 recruitment is pivotal to TH-17 immunity by selective activation of NF-κB subunit c-Rel, which induces expression of TH-17-polarizing cytokines IL-1β and IL-23p19. Malt1 inhibition abrogates c-Rel activation and TH-17 immunity to Candida species. We found that Malt1-mediated activation of c-Rel is similarly essential to induction of TH-17-polarizing cytokines by dectin-2. Whereas dectin-1 activates all NF-κB subunits, dectin-2 selectively activates c-Rel, signifying a specialized TH-17-enhancing function for dectin-2 in anti-fungal immunity by human dendritic cells. Thus, dectin-1 and dectin-2 control adaptive TH-17 immunity to fungi via Malt1-dependent activation of c-Rel.

【 授权许可】

CC BY