Redundant roles for inflammasome receptors NLRP3 and NLRC4 in host defense against Salmonella

Broz, Petr and Newton, Kim and Lamkanfi, Mohamed and Mariathasan, Sanjeev and Dixit, Vishva M. and Monack, Denise M.. (2010) Redundant roles for inflammasome receptors NLRP3 and NLRC4 in host defense against Salmonella. Journal of Experimental Medicine, 207 (8). pp. 1745-1755.

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Intracellular pathogens and endogenous danger signals in the cytosol engage NOD-like receptors (NLRs), which assemble inflammasome complexes to activate caspase-1 and promote the release of proinflammatory cytokines IL-1beta and IL-18. However, the NLRs that respond to microbial pathogens in vivo are poorly defined. We show that the NLRs NLRP3 and NLRC4 both activate caspase-1 in response to Salmonella typhimurium. Responding to distinct bacterial triggers, NLRP3 and NLRC4 recruited ASC and caspase-1 into a single cytoplasmic focus, which served as the site of pro-IL-1beta processing. Consistent with an important role for both NLRP3 and NLRC4 in innate immune defense against S. typhimurium, mice lacking both NLRs were markedly more susceptible to infection. These results reveal unexpected redundancy among NLRs in host defense against intracellular pathogens in vivo.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Infection Biology
UniBasel Contributors:Broz, Petr
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Rockefeller University Press
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:29 Nov 2017 11:04
Deposited On:29 Nov 2017 11:04

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