Salmonella infection induces recruitment of Caspase-8 to the inflammasome to modulate IL-1β production

Si Ming Man, Panagiotis Tourlomousis, Lee Hopkins, Tom P. Monie, Katherine A. Fitzgerald, Clare E. Bryant*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

192 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)5239-5246
Number of pages8
JournalJournal of Immunology
Volume191
Issue number10
DOIs
Publication statusPublished - 15 Nov 2013
Externally publishedYes

Fingerprint

Dive into the research topics of 'Salmonella infection induces recruitment of Caspase-8 to the inflammasome to modulate IL-1β production'. Together they form a unique fingerprint.

Cite this