Article abstract
Nature Immunology 8, 198 - 205 (2006)
Published online: 24 December 2006 | doi:10.1038/ni1426
The adaptor protein CARD9 is required for innate immune responses to intracellular pathogens
Yen-Michael S Hsu1, Yongliang Zhang2, Yun You1, Donghai Wang3, Hongxiu Li1, Omar Duramad2, Xiao-Feng Qin2, Chen Dong2 & Xin Lin1
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-
B 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.
- Department of Molecular and Cellular Oncology, University of Texas, M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
- Department of Immunology, University of Texas, M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
- The CBR Institute for Biomedical Research, Harvard Medical School, Boston, Massachusetts 02115, USA.
Correspondence to: Xin Lin1 e-mail: xllin@mdanderson.org
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