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

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

doi:10.1038/ni1426

Cited by 375 publications

(413 citation statements)

References 33 publications

(75 reference statements)

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“…18 NOD1 and NOD2 also engage CARD9, which mediates the activation of mitogen-activated protein kinase cascades responsible for nuclear translocation of Jun and ATF2 transcription factors. 19 NF-kB and mitogen-activated protein kinase-mediated pathways trigger a vigorous inflammatory response characterized by secretion of proinflammatory cytokines and chemokines.…”

Section: The Nlr Familymentioning

confidence: 99%

The inflammasomes in health and disease: from genetics to molecular mechanisms of autoinflammation and beyond

2011

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Nucleotide-binding oligomerization domain (NOD)-containing protein-like receptors (NLRs) are a recently discovered class of innate immune receptors that play a crucial role in initiating the inflammatory response following pathogen recognition. Some NLRs form the framework for cytosolic platforms called inflammasomes, which orchestrate the early inflammatory process via IL-1b activation. Mutations and polymorphisms in NLR-coding genes or in genetic loci encoding inflammasome-related proteins correlate with a variety of autoinflammatory diseases. Moreover, the activity of certain inflammasomes is associated with susceptibility to infections as well as autoimmunity and tumorigenesis. In this review, we will discuss how identifying the genetic characteristics of inflammasomes is assisting our understanding of both autoinflammatory diseases as well as other immune system-driven disorders.

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Section: The Nlr Familymentioning

confidence: 99%

The inflammasomes in health and disease: from genetics to molecular mechanisms of autoinflammation and beyond

2011

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“…Several studies also demonstrate that CARD9 is involved in immunity to intracellular bacteria Listeria monocytogenes [7,150,159] and Mycobacteruim tuberculosis [160]. The latest work suggests that CARD9 controls the production of reactive oxygen species (ROS) by regulating the LyGDI-Rac1 complex following the phagocytosis of microorganisms by macrophages [159].…”

Section: Other Functions Of Card9mentioning

confidence: 99%

“…It was identified through a database search for CARD-containing proteins and shown to interact with Bcl10 [148]. Its expression seems to be restricted to myeloid cells, mainly macrophages, dendritic cells and neutrophils [148][149][150]. Although CARD9 is structurally related to the CARMA family, it lacks the C-terminal MAGUK domain (Figure 2) that determinates plasma membrane localization.…”

Section: Card9-mediated Nf-κb Signaling Pathwaysmentioning

confidence: 99%

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NF-κB signaling pathways regulated by CARMA family of scaffold proteins

Blonska¹,

Lin²

2010

Cell Res

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173

201

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The NF-κB family of transcription factors plays a crucial role in cell activation, survival and proliferation. Its aberrant activity results in cancer, immunodeficiency or autoimmune disorders. Over the past two decades, tremendous progress has been made in our understanding of the signals that regulate NF-κB activation, especially how scaffold proteins link different receptors to the NF-κB-activating complex, the IκB kinase complex. The growing number of these scaffolds underscores the complexity of the signaling networks in different cell types. In this review, we discuss the role of scaffold molecules in signaling cascades induced by stimulation of antigen receptors, G-protein-coupled receptors and C-type Lectin receptors, resulting in NF-κB activation. Especially, we focus on the family of Caspase recruitment domain (CARD)-containing proteins known as CARMA and their function in activation of NF-κB, as well as the link of these scaffolds to the development of various neoplastic diseases through regulation of NF-κB.

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“…CARD9 is closely associated with immune responses, immune cell activation 3, 4 and inflammatory response 5. CARD9 utilizes B‐Cell lymphoma 10 (BCL10) and MALT1 to mediate Dectin‐1 signalling for the activation of nuclear factor‐k‐gene binding (NF‐κB), p38 mitogen‐activated protein kinase (p38 MAPK), and c‐Jun N‐terminal kinase (JNK) 2, 3.…”

Section: Introductionmentioning

confidence: 99%

The essential function of CARD9 in diet‐induced inflammation and metabolic disorders in mice

Zeng

Zhang

et al. 2018

J Cellular Molecular Medi

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Inflammation and metabolic disorder are common pathophysiological conditions, which play a vital role in the development of obesity and type 2 diabetes. The purpose of this study was to explore the effects of caspase recruitment domain (CARD) 9 in the high fat diet (HFD)‐treated mice and attempt to find a molecular therapeutic target for obesity development and treatment. Sixteen male CARD9−/− and corresponding male WT mice were fed with normal diet or high fat diet, respectively, for 12 weeks. Glucose tolerance, insulin resistance, oxygen consumption and heat production of the mice were detected. The CARD9/MAPK pathway‐related gene and protein were determined in insulin‐responsive organs using Western blotting and quantitative PCR. The results showed that HFD‐induced insulin resistance and impairment of glucose tolerance were more severe in WT mice than that in the CARD9−/− mice. CARD9 absence significantly modified O2 consumption, CO 2 production and heat production. CARD9−/− mice displayed the lower expression of p38 MAPK, JNK and ERK when compared to the WT mice in both HFD‐ and ND‐treated groups. HFD induced the increase of p38 MAPK, JNK and ERK in WT mice but not in the CARD9−/− mice. The results indicated that CARD9 absence could be a vital protective factor in diet‐induced obesity via the CARD9/MAPK pathway, which may provide new insights into the development of gene knockout to improving diet‐induced obesity and metabolism disorder.

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

Cited by 375 publications

References 33 publications

The inflammasomes in health and disease: from genetics to molecular mechanisms of autoinflammation and beyond

The inflammasomes in health and disease: from genetics to molecular mechanisms of autoinflammation and beyond

NF-κB signaling pathways regulated by CARMA family of scaffold proteins

The essential function of CARD9 in diet‐induced inflammation and metabolic disorders in mice

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