CARD9 negatively regulates NLRP3-induced IL-1β production upon Salmonella infection of macrophages
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Pereira, M., Tourlomousis, P., Wright, J., Monie, T., & Bryant, C. (2016). CARD9 negatively regulates NLRP3-induced IL-1β production upon Salmonella infection of macrophages. Nature Communications, 7 (12874)https://doi.org/10.1038/ncomms12874
Interleukin 1b (IL-1b) is a pro-inflammatory cytokine required for host control of bacterial infections. Its production must be tightly regulated to prevent excessive inflammation. Here we identify a surprising negative regulatory role for caspase recruitment domain-containing protein 9 (CARD9), a protein associated with induction of pro-inflammatory cytokines by fungi, on IL-1b production during bacterial infection. CARD9 negatively regulates IL-1β production in response to activation of the nucleotide oligomerization domain receptor pyrin-domain containing protein 3 (NLRP3) by Salmonella infection by fine-tuning pro-IL-1β expression, reducing spleen tyrosine kinase-mediated NLRP3 activation and repressing inflammasome associated caspase-8 activity. CARD9 is suppressed during Salmonella infection facilitating increased IL-1β production. CARD9 is, therefore, a central signaling hub that co-ordinates a pathogen specific host inflammatory response.
Is supplemented by: https://doi.org/10.17863/CAM.778
M.P. was supported by CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Brazil). This work was supported by a grant from the BBSRC BB/K006436/1 and a Wellcome Trust Investigator award to CEB.
WELLCOME TRUST (108045/Z/15/Z)
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External DOI: https://doi.org/10.1038/ncomms12874
This record's URL: https://www.repository.cam.ac.uk/handle/1810/257338
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