PT  - JOURNAL ARTICLE
AU  - Man, Si Ming
AU  - Tourlomousis, Panagiotis
AU  - Hopkins, Lee
AU  - Monie, Tom P.
AU  - Fitzgerald, Katherine A.
AU  - Bryant, Clare E.
TI  - <em>Salmonella</em> Infection Induces Recruitment of Caspase-8 to the Inflammasome To Modulate IL-1β Production
AID  - 10.4049/jimmunol.1301581
DP  - 2013 Nov 15
TA  - The Journal of Immunology
PG  - 5239--5246
VI  - 191
IP  - 10
4099  - http://www.jimmunol.org/content/191/10/5239.short
4100  - http://www.jimmunol.org/content/191/10/5239.full
SO  - J. Immunol.2013 Nov 15; 191
AB  - Nucleotide-binding oligomerization domain–like receptors (NLRs) detect pathogens and danger-associated signals within the cell. Salmonella enterica serovar Typhimurium, an intracellular pathogen, activates caspase-1 required for the processing of the proinflammatory cytokines, pro–IL-1β and pro–IL-18, and pyroptosis. In this study, we show that Salmonella infection induces the formation of an apoptosis-associated specklike protein containing a CARD (ASC)–Caspase-8–Caspase-1 inflammasome in macrophages. Caspase-8 and caspase-1 are recruited to the ASC focus independently of one other. Salmonella infection initiates caspase-8 proteolysis in a manner dependent on NLRC4 and ASC, but not NLRP3, caspase-1 or caspase-11. Caspase-8 primarily mediates the synthesis of pro-IL-1β, but is dispensable for Salmonella-induced cell death. Overall, our findings highlight that the ASC inflammasome can recruit different members of the caspase family to induce distinct effector functions in response to Salmonella infection.