Card9 controls a non-TLR signalling pathway for innate anti-fungal immunity

Fungal infections are increasing worldwide due to the marked rise in immunodeficiencies including AIDS; however, immune responses to fungi are poorly understood. Dectin-1 is the major mammalian pattern recognition receptor for the fungal component zymosan. Dectin-1 represents the prototype of innate...

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Bibliographic Details
Published in:Nature 2006-08, Vol.442 (7103), p.651-656
Main Authors: Ruland, Jürgen, Gross, Olaf, Gewies, Andreas, Finger, Katrin, Schäfer, Martin, Sparwasser, Tim, Peschel, Christian, Förster, Irmgard
Format: Article
Language:English
Subjects:
Adaptor Proteins, Signal Transducing - deficiency
Adaptor Proteins, Signal Transducing - genetics
Adaptor Proteins, Signal Transducing - immunology
Adaptor Proteins, Signal Transducing - metabolism
Animals
Antigens, Fungal - immunology
B-Cell CLL-Lymphoma 10 Protein
Biological and medical sciences
Candida albicans - immunology
CARD Signaling Adaptor Proteins
Caspases - metabolism
Cell physiology
Cytokines
Cytokines - biosynthesis
Cytokines - immunology
Fundamental and applied biological sciences. Psychology
Fungal infections
Fungi - immunology
Immune system
Immunity, Innate - immunology
Intracellular Signaling Peptides and Proteins - metabolism
Lectins, C-Type
Lymphocyte Activation - immunology
Membrane Proteins - metabolism
Mice
Molecular and cellular biology
Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein
Neoplasm Proteins - metabolism
Nerve Tissue Proteins - metabolism
NF-kappa B - metabolism
Protein-Tyrosine Kinases - metabolism
Proteins
Signal Transduction
Syk Kinase
Toll-Like Receptors
Zymosan - immunology
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Summary:Fungal infections are increasing worldwide due to the marked rise in immunodeficiencies including AIDS; however, immune responses to fungi are poorly understood. Dectin-1 is the major mammalian pattern recognition receptor for the fungal component zymosan. Dectin-1 represents the prototype of innate non-Toll-like receptors (TLRs) containing immunoreceptor tyrosine-based activation motifs (ITAMs) related to those of adaptive antigen receptors. Here we identify Card9 as a key transducer of Dectin-1 signalling. Although being dispensable for TLR/MyD88-induced responses, Card9 controls Dectin-1-mediated myeloid cell activation, cytokine production and innate anti-fungal immunity. Card9 couples to Bcl10 and regulates Bcl10-Malt1-mediated NF-kappaB activation induced by zymosan. Yet, Card9 is dispensable for antigen receptor signalling that uses Carma1 as a link to Bcl10-Malt1. Thus, our results define a novel innate immune pathway and indicate that evolutionarily distinct ITAM receptors in innate and adaptive immune cells use diverse adaptor proteins to engage selectively the conserved Bcl10-Malt1 module.
ISSN:0028-0836
1476-4687
1476-4679
DOI:10.1038/nature04926