10.17863/CAM.7071
Pereira, Milton
Tourlomousis, Panagiotis
0000-0002-6152-8066
Wright, John
0000-0002-9758-9944
Monie, Tom
Bryant, Clare
0000-0002-2924-0038
CARD9 negatively regulates NLRP3-induced IL-1β production upon Salmonella infection of macrophages
Apollo - University of Cambridge Repository (staging)
2016
Apollo - University of Cambridge Repository (staging)
Apollo - University of Cambridge Repository (staging)
2016-09-27
Article
2041-1723
2041-1723
10.17863/CAM.778
Attribution 4.0 International
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.
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.
This is the final version of the article. It first appeared from Nature Publishing Group via http://doi.org.10.1038/ncomms12874.