title: The adaptor protein CARD9 is required for innate immune responses to intracellular pathogens.
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.
authors.affiliation: Department of Molecular and Cellular Oncology, University of Texas, M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Yen-Michael S
authors.initials: YM
authors.lastname: Hsu
authors.forename: Yongliang
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yun
authors.initials: Y
authors.lastname: You
authors.forename: Donghai
authors.initials: D
authors.lastname: Wang
authors.forename: Hongxiu
authors.initials: H
authors.lastname: Li
authors.forename: Omar
authors.initials: O
authors.lastname: Duramad
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Qin
authors.forename: Chen
authors.initials: C
authors.lastname: Dong
authors.forename: Xin
authors.initials: X
authors.lastname: Lin
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000172:deficiency / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D000818:Animals; D053468:CARD Signaling Adaptor Proteins; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004789:Enzyme Activation; D015870:Gene Expression; D007113:Immunity, Innate / Q000276:immunology*; D042541:Intracellular Space / Q000382:microbiology*; D008024:Ligands; D008089:Listeria monocytogenes / Q000276:immunology* / Q000502:physiology; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism; D053473:Nod2 Signaling Adaptor Protein / Q000378:metabolism; D011485:Protein Binding; D053475:Receptor-Interacting Protein Serine-Threonine Kinase 2 / Q000378:metabolism; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D053468:CARD Signaling Adaptor Proteins; C513280:Card9 protein, mouse; D016207:Cytokines; D008024:Ligands; D016328:NF-kappa B; D053473:Nod2 Signaling Adaptor Protein; C495945:Nod2 protein, mouse; D053475:Receptor-Interacting Protein Serine-Threonine Kinase 2; D048051:p38 Mitogen-Activated Protein Kinases