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Hsu, Y. M. et al. The adaptor protein CARD9 is required for innate immune responses to intracellular pathogens. Nat. Immunol. 8, 198-205

Department of Molecular and Cellular Oncology, University of Texas, M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
Nature Immunology (Impact Factor: 24.97). 03/2007; 8(2):198-205. DOI: 10.1038/ni1426
Source: PubMed

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.

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    • "(2014), http://dx.doi.org/10.1016/j.febslet.2014.06.035 dipeptide or Listeria monocytogenes [17]. The association between NOD2 and CARD9 was enhanced by the presence of RIP2 in both over-expression and endogenous systems [17]. The relationship between CARD9 and NOD2 is particularly intriguing as the genes for both these proteins contain polymorphisms influencing susceptibility to Crohn's Disease in humans [18] [19]. "
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    FEBS Letters 06/2014; 588(17). DOI:10.1016/j.febslet.2014.06.035 · 3.34 Impact Factor
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    • "RIPK2 is critical for NOD1- and NOD2-mediated NF-KB activation because NOD1 and NOD2 signaling is abolished in RIPK2-deficient cells [41]. In addition to the activation of the NF-KB pathway, NOD2 stimulation results in activation of the MAPKs p38, ERK and JNK [42]. 2) Alternative pathways which may or may not require RIPK2 include the induction of type I IFN and autophagy [24], [43]–[45]. "
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    • "NOD-like receptor pathway adaptor protein, CARD9 was up regulated in all three groups (Figure 7 and 8). CARD9 plays a critical role in NOD2-mediated regulation of NF-κB and MAP kinase signaling leading to pro-inflammatory responses (Table S5) [23], [24]. Alteration of certain genes resulting in inhibition or regulation of NF-κB was observed as in case of CHUK (conserved helix-loop-helix ubiquitous kinase)/IKK1. "
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