PMID:17187069

Citation	Hsu, YM, Zhang, Y, You, Y, Wang, D, Li, H, Duramad, O, Qin, XF, Dong, C and Lin, X (2007) The adaptor protein CARD9 is required for innate immune responses to intracellular pathogens. Nat. Immunol. 8:198-205
Abstract	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.
Links	PubMed Online version:10.1038/ni1426
Keywords	Adaptor Proteins, Signal Transducing/deficiency; Adaptor Proteins, Signal Transducing/genetics; Adaptor Proteins, Signal Transducing/immunology; Adaptor Proteins, Signal Transducing/metabolism; Animals; Cells, Cultured; Cytokines/metabolism; Enzyme Activation; Gene Expression; Immunity, Innate/immunology; Intracellular Space/microbiology; Ligands; Listeria monocytogenes/immunology; Listeria monocytogenes/physiology; Macrophages/metabolism; Mice; Mice, Inbred C57BL; Mice, Knockout; NF-kappa B/metabolism; Nod2 Signaling Adaptor Protein/metabolism; Protein Binding; Receptor-Interacting Protein Serine-Threonine Kinase 2/metabolism; Signal Transduction; p38 Mitogen-Activated Protein Kinases/metabolism
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