Selective C-Rel activation via Malt1 controls anti-fungal T(H)-17 immunity by dectin-1 and dectin-2

Sonja I Gringhuis; Brigitte A Wevers; Tanja M Kaptein; Toni M M van Capel; Bart Theelen; Teun Boekhout; Esther C de Jong; Teunis B H Geijtenbeek

doi:10.1371/journal.ppat.1001259

Selective C-Rel activation via Malt1 controls anti-fungal T(H)-17 immunity by dectin-1 and dectin-2

Sonja I Gringhuis, Brigitte A Wevers, Tanja M Kaptein, Toni M M van Capel, Bart Theelen, Teun Boekhout, Esther C de Jong, Teunis B H Geijtenbeek

Research output: Contribution to journal › Article › Academic › peer-review

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.

Original language	English
Article number	e1001259
Journal	PLoS Pathogens
Volume	7
Issue number	1
DOIs	https://doi.org/10.1371/journal.ppat.1001259
Publication status	Published - 2011
Externally published	Yes

Keywords

Adaptive Immunity/immunology
Candida/immunology
Caspase Inhibitors
Caspases/genetics
Cells, Cultured
DNA-Binding Proteins/genetics
Dendritic Cells/immunology
Gene Expression Regulation
Humans
Interleukin-1beta/metabolism
Interleukin-23 Subunit p19/metabolism
Lectins, C-Type/genetics
Membrane Proteins/genetics
Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein
Neoplasm Proteins/antagonists & inhibitors
Nerve Tissue Proteins/genetics
Nuclear Proteins/genetics
Proto-Oncogene Proteins c-rel
Th17 Cells/immunology

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10.1371/journal.ppat.1001259

http://www.ncbi.nlm.nih.gov/pubmed/21283787

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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.",

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author = "Gringhuis, {Sonja I} and Wevers, {Brigitte A} and Kaptein, {Tanja M} and {van Capel}, {Toni M M} and Bart Theelen and Teun Boekhout and {de Jong}, {Esther C} and Geijtenbeek, {Teunis B H}",

year = "2011",

doi = "10.1371/journal.ppat.1001259",

language = "English",

volume = "7",

journal = "PLoS Pathogens",

issn = "1553-7366",

publisher = "Public Library of Science",

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T1 - Selective C-Rel activation via Malt1 controls anti-fungal T(H)-17 immunity by dectin-1 and dectin-2

AU - Gringhuis, Sonja I

AU - Wevers, Brigitte A

AU - Kaptein, Tanja M

AU - van Capel, Toni M M

AU - Theelen, Bart

AU - Boekhout, Teun

AU - de Jong, Esther C

AU - Geijtenbeek, Teunis B H

PY - 2011

Y1 - 2011

N2 - 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.

AB - 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.

KW - Adaptive Immunity/immunology

KW - Candida/immunology

KW - Caspase Inhibitors

KW - Caspases/genetics

KW - Cells, Cultured

KW - DNA-Binding Proteins/genetics

KW - Dendritic Cells/immunology

KW - Gene Expression Regulation

KW - Humans

KW - Interleukin-1beta/metabolism

KW - Interleukin-23 Subunit p19/metabolism

KW - Lectins, C-Type/genetics

KW - Membrane Proteins/genetics

KW - Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein

KW - Neoplasm Proteins/antagonists & inhibitors

KW - Nerve Tissue Proteins/genetics

KW - Nuclear Proteins/genetics

KW - Proto-Oncogene Proteins c-rel

KW - Th17 Cells/immunology

U2 - 10.1371/journal.ppat.1001259

DO - 10.1371/journal.ppat.1001259

M3 - Article

C2 - 21283787

SN - 1553-7366

VL - 7

JO - PLoS Pathogens

JF - PLoS Pathogens

IS - 1

M1 - e1001259

ER -

Selective C-Rel activation via Malt1 controls anti-fungal T(H)-17 immunity by dectin-1 and dectin-2

Abstract

Keywords

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