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The adaptor protein CARD9 is required for innate immune responses to intracellular pathogens.

The caspase-recruitment domain-containing adaptor protein CARD9 regulates the innate signaling responses to fungal infection. Here we show that CARD9 is required for innate immune responses against intracellular pathogens. We generated Card9(-/-) mice and found that CARD9-deficient macrophages had defects in activation of the kinases p38 and Jnk but not of transcription factor NF-kappaB after bacterial and viral infection. CARD9-deficient mice failed to clear infection and showed altered cytokine production after challenge with Listeria monocytogenes. In wild-type cells, we found CARD9 inducibly associated with both the intracellular 'biosensor' Nod2 and the serine-threonine kinase RICK. Our data demonstrate that CARD9 has a critical function in Nod2-mediated activation of p38 and Jnk in innate immune responses to intracellular pathogens.

Pubmed ID: 17187069

Authors

  • Hsu YM
  • Zhang Y
  • You Y
  • Wang D
  • Li H
  • Duramad O
  • Qin XF
  • Dong C
  • Lin X

Journal

Nature immunology

Publication Data

February 23, 2007

Associated Grants

None

Mesh Terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • CARD Signaling Adaptor Proteins
  • Cells, Cultured
  • Cytokines
  • Enzyme Activation
  • Gene Expression
  • Immunity, Innate
  • Intracellular Space
  • Ligands
  • Listeria monocytogenes
  • Macrophages
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • NF-kappa B
  • Nod2 Signaling Adaptor Protein
  • Protein Binding
  • Receptor-Interacting Protein Serine-Threonine Kinase 2
  • Signal Transduction
  • p38 Mitogen-Activated Protein Kinases