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

被引:356
作者
Hsu, Yen-Michael S.
Zhang, Yongliang
You, Yun
Wang, Donghai
Li, Hongxiu
Duramad, Omar
Qin, Xiao-Feng
Dong, Chen
Lin, Xin [1 ]
机构
[1] Univ Texas, MD Anderson Canc Ctr, Dept Mol & Cellular Oncol, Houston, TX 77030 USA
[2] Univ Texas, MD Anderson Canc Ctr, Dept Immunol, Houston, TX 77030 USA
[3] Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA
基金
美国国家卫生研究院;
关键词
D O I
10.1038/ni1426
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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-kappa 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.
引用
收藏
页码:198 / 205
页数:8
相关论文
共 33 条
  • [1] Pathogen recognition and innate immunity
    Akira, S
    Uematsu, S
    Takeuchi, O
    [J]. CELL, 2006, 124 (04) : 783 - 801
  • [2] Toll-like receptor signalling
    Akira, S
    Takeda, K
    [J]. NATURE REVIEWS IMMUNOLOGY, 2004, 4 (07) : 499 - 511
  • [3] Recognition of double-stranded RNA and activation of NF-κB by Toll-like receptor 3
    Alexopoulou, L
    Holt, AC
    Medzhitov, R
    Flavell, RA
    [J]. NATURE, 2001, 413 (6857) : 732 - 738
  • [4] The many paths to p38 mitogen-activated protein kinase activation in the immune system
    Ashwell, Jonathan D.
    [J]. NATURE REVIEWS IMMUNOLOGY, 2006, 6 (07) : 532 - 540
  • [5] CARD9 is a novel caspase recruitment domain-containing protein that interacts with BCL10/CLAP and activates NF-κB
    Bertin, J
    Guo, Y
    Wang, L
    Srinivasula, SM
    Jacobson, MD
    Poyet, JL
    Merriam, S
    Du, MQ
    Dyer, MJS
    Robison, KE
    DiStefano, PS
    Alnemri, ES
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (52) : 41082 - 41086
  • [6] Involvement of receptor-interacting protein 2 in innate and adaptive immune responses
    Chin, AI
    Dempsey, PW
    Bruhn, K
    Miller, JF
    Xu, Y
    Cheng, GH
    [J]. NATURE, 2002, 416 (6877) : 190 - 194
  • [7] MAP kinases in the immune response
    Dong, C
    Davis, RJ
    Flavell, RA
    [J]. ANNUAL REVIEW OF IMMUNOLOGY, 2002, 20 : 55 - 72
  • [8] IL-10 regulates plasmacytoid dendritic cell response to CpG-containing immunostimulatory sequences
    Duramad, O
    Fearon, KL
    Chan, JH
    Kanzler, H
    Marshall, JD
    Coffman, RL
    Barrat, FJ
    [J]. BLOOD, 2003, 102 (13) : 4487 - 4492
  • [9] MyD88-dependent but Toll-like receptor 2-independent innate immunity to Listeria:: No role for either in macrophage listericidal activity
    Edelson, BT
    Unanue, ER
    [J]. JOURNAL OF IMMUNOLOGY, 2002, 169 (07) : 3869 - 3875
  • [10] LPS-TLR4 signaling to IRF-3/7 and NF-κB involves the toll adapters TRAM and TRIF
    Fitzgerald, KA
    Rowe, DC
    Barnes, BJ
    Caffrey, DR
    Visintin, A
    Latz, E
    Monks, B
    Pitha, PM
    Golenbock, DT
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 2003, 198 (07) : 1043 - 1055