title: Selective C-Rel activation via Malt1 controls anti-fungal T(H)-17 immunity by dectin-1 and dectin-2.
abstract: C-type lectins dectin-1 and dectin-2 on dendritic cells elicit protective immunity against fungal infections through induction of T(H)1 and T(H)-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 T(H)-17 immunity by selective activation of NF-κB subunit c-Rel, which induces expression of T(H)-17-polarizing cytokines IL-1β and IL-23p19. Malt1 inhibition abrogates c-Rel activation and T(H)-17 immunity to Candida species. We found that Malt1-mediated activation of c-Rel is similarly essential to induction of T(H)-17-polarizing cytokines by dectin-2. Whereas dectin-1 activates all NF-κB subunits, dectin-2 selectively activates c-Rel, signifying a specialized T(H)-17-enhancing function for dectin-2 in anti-fungal immunity by human dendritic cells. Thus, dectin-1 and dectin-2 control adaptive T(H)-17 immunity to fungi via Malt1-dependent activation of c-Rel.
authors.affiliation: Center of Infection and Immunity Amsterdam and Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. s.i.gringhuis@amc.uva.nl
authors.forename: Sonja I
authors.initials: SI
authors.lastname: Gringhuis
authors.forename: Brigitte A
authors.initials: BA
authors.lastname: Wevers
authors.forename: Tanja M
authors.initials: TM
authors.lastname: Kaptein
authors.forename: Toni M M
authors.initials: TM
authors.lastname: van Capel
authors.forename: Bart
authors.initials: B
authors.lastname: Theelen
authors.forename: Teun
authors.initials: T
authors.lastname: Boekhout
authors.forename: Esther C
authors.initials: EC
authors.lastname: de Jong
authors.forename: Teunis B H
authors.initials: TB
authors.lastname: Geijtenbeek
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology; D002175:Candida / Q000276:immunology; D061945:Caspase Inhibitors; D020169:Caspases / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D053760:Interleukin-23 Subunit p19 / Q000378:metabolism; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D000074884:Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D020569:Proto-Oncogene Proteins c-rel; D058504:Th17 Cells / Q000276:immunology*; D000099181:Dectin-1
chemical_list: D061945:Caspase Inhibitors; D020169:Caspases; D004268:DNA-Binding Proteins; D053583:Interleukin-1beta; D053760:Interleukin-23 Subunit p19; D037181:Lectins, C-Type; D008565:Membrane Proteins; D000074884:Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D020569:Proto-Oncogene Proteins c-rel; D000099181:Dectin-1; C068059:REL protein, human; C445340:dectin-2, mouse; C400109:MALT1 protein, human