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

Yen-Michael S Hsu; Yongliang Zhang; Yun You; Donghai Wang; Hongxiu Li; Omar Duramad; Xiao-Feng Qin; Chen Dong; Xin Lin

doi:10.1038/ni1426

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

Nat Immunol. 2007 Feb;8(2):198-205. doi: 10.1038/ni1426. Epub 2006 Dec 24.

Authors

Yen-Michael S Hsu¹, Yongliang Zhang, Yun You, Donghai Wang, Hongxiu Li, Omar Duramad, Xiao-Feng Qin, Chen Dong, Xin Lin

Affiliation

¹ Department of Molecular and Cellular Oncology, University of Texas, M.D. Anderson Cancer Center, Houston, Texas 77030, USA.

PMID: 17187069
DOI: 10.1038/ni1426

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adaptor Proteins, Signal Transducing / deficiency
Adaptor Proteins, Signal Transducing / genetics
Adaptor Proteins, Signal Transducing / immunology*
Adaptor Proteins, Signal Transducing / metabolism*
Animals
CARD Signaling Adaptor Proteins
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

Substances

Adaptor Proteins, Signal Transducing
CARD Signaling Adaptor Proteins
Card9 protein, mouse
Cytokines
Ligands
NF-kappa B
Nod2 Signaling Adaptor Protein
Nod2 protein, mouse
Receptor-Interacting Protein Serine-Threonine Kinase 2
p38 Mitogen-Activated Protein Kinases