Interleukin 1β (IL-1β) is a pro-inflammatory cytokine required for host control of bacterial infections, and its production must be tightly regulated to prevent excessive inflammation. Here we identify show a surprising negative regulatory role for caspase recruitment domain-containing protein 9 (CARD9), a protein associated with induction of pro-inflammatory cytokines by fungi, has a negative role on IL-1β production during bacterial infection. CARD9 negatively regulates IL-1β productionSpecifically, in response to activation of the nucleotide oligomerization domain receptor pyrin-domain containing protein 3 (NLRP3) by Salmonella infection, CARD9 negatively regulates IL-1β by fine-tuning pro-IL-1β expression, reducing SYK-mediated NLRP3 activation and repressing inflammasome inflammasome-associated caspase-8 activity. CARD9 is suppressed during Salmonella enterica serovar Typhimurium infection, facilitating increased IL-1β production. CARD9 is, therefore, a central signalling hub that co-ordinates a pathogen- specific host inflammatory response.BBSRC [BB/K006436/1], Wellcome Trust [Investigator 108045/Z/15/Z], CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Brazil
