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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 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.

Pubmed ID: 16862125

Authors

  • Gross O
  • Gewies A
  • Finger K
  • Schäfer M
  • Sparwasser T
  • Peschel C
  • Förster I
  • Ruland J

Journal

Nature

Publication Data

August 10, 2006

Associated Grants

None

Mesh Terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Antigens, Fungal
  • CARD Signaling Adaptor Proteins
  • Candida albicans
  • Caspases
  • Cytokines
  • Fungi
  • Immunity, Innate
  • Intracellular Signaling Peptides and Proteins
  • Lectins, C-Type
  • Lymphocyte Activation
  • Membrane Proteins
  • Mice
  • NF-kappa B
  • Neoplasm Proteins
  • Nerve Tissue Proteins
  • Protein-Tyrosine Kinases
  • Signal Transduction
  • Toll-Like Receptors
  • Zymosan