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

• Published in: Nature Immunology Vol. 8; no. 2; pp. 198 - 205
• Main Authors: Lin, Xin, Hsu, Yen-Michael S, Zhang, Yongliang, You, Yun, Wang, Donghai, Li, Hongxiu, Duramad, Omar, Qin, Xiao-Feng, Dong, Chen
• Format: Journal Article
• Language: English
• Published: United States Nature Publishing Group 01-02-2007
• Subjects: Adaptor Proteins, Signal Transducing - deficiency; Adaptor Proteins, Signal Transducing - genetics; Adaptor Proteins, Signal Transducing - immunology; Adaptor Proteins, Signal Transducing - metabolism; Animals; Biosensors; CARD Signaling Adaptor Proteins; Cells, Cultured; Cellular signal transduction; Cytokines - metabolism; Development and progression; Enzyme Activation; Evaluation; Gene Expression; Health aspects; Immune response; Immunity, Innate - immunology; Infection; Intracellular Space - microbiology; Ligands; Listeria monocytogenes; Listeria monocytogenes - immunology; Listeria monocytogenes - physiology; Macrophages - metabolism; Mice; Mice, Inbred C57BL; Mice, Knockout; NF-kappa B - metabolism; Nod2 Signaling Adaptor Protein - metabolism; p38 Mitogen-Activated Protein Kinases - metabolism; Pathogens; Properties; Protein Binding; Proteins; Receptor-Interacting Protein Serine-Threonine Kinase 2 - metabolism; Signal Transduction; United States
• ISSN: 1529-2908; 1529-2916; 1365-2567
• DOI: 10.1038/ni1426

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.