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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptive Immunity / immunology
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Candida / immunology
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Caspase Inhibitors
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Caspases / genetics
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Caspases / metabolism*
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Cells, Cultured
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Dendritic Cells / immunology*
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Dendritic Cells / metabolism
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Gene Expression Regulation
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Humans
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Interleukin-1beta / metabolism
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Interleukin-23 Subunit p19 / metabolism
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Lectins, C-Type / genetics
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Lectins, C-Type / metabolism*
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Membrane Proteins / genetics
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Membrane Proteins / metabolism*
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Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein
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Neoplasm Proteins / antagonists & inhibitors
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Neoplasm Proteins / genetics
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Neoplasm Proteins / metabolism*
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism*
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism*
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Proto-Oncogene Proteins c-rel
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Th17 Cells / immunology*
Substances
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Caspase Inhibitors
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DNA-Binding Proteins
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Interleukin-1beta
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Interleukin-23 Subunit p19
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Lectins, C-Type
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Membrane Proteins
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Neoplasm Proteins
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Nerve Tissue Proteins
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Nuclear Proteins
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Proto-Oncogene Proteins c-rel
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REL protein, human
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dectin 1
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dectin-2, mouse
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Caspases
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MALT1 protein, human
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Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein