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

Olaf Gross, Andreas Gewies, Katrin Finger, Martin Schäfer, Tim Sparwasser, Christian Peschel, Irmgard Förster and Jürgen Ruland ()
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Olaf Gross: Technische Universität München
Andreas Gewies: Technische Universität München
Katrin Finger: Technische Universität München
Martin Schäfer: Technische Universität München
Tim Sparwasser: Technische Universität München
Christian Peschel: Technische Universität München
Irmgard Förster: Technische Universität München
Jürgen Ruland: Technische Universität München

Nature, 2006, vol. 442, issue 7103, 651-656

Abstract: Abstract 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-κB 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.

Date: 2006
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DOI: 10.1038/nature04926

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