Salmonella exploits NLRP12-dependent innate immune signaling to suppress host defenses during infection

Md Hasan Zaki, Si Ming Man, Peter Vogel, Mohamed Lamkanfi, Thirumala Devi Kanneganti

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

The nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain containing 12 (NLRP12) plays a protective role in intestinal inflammation and carcinogenesis, but the physiological function of this NLR during microbial infection is largely unexplored. Salmonella enterica serovar Typhimurium (S. typhimurium) is a leading cause of food poisoning worldwide. Here, we show that NLRP12-deficient mice were highly resistant to S. typhimurium infection. Salmonella-infected macrophages induced NLRP12-dependent inhibition of NF-κB and ERK activation by suppressing phosphorylation of IκBα and ERK. NLRP12-mediated downregulation of proinflammatory and antimicrobial molecules prevented efficient clearance of bacterial burden, highlighting a role for NLRP12 as a negative regulator of innate immune signaling during salmonellosis. These results underscore a signaling pathway defined by NLRP12-mediated dampening of host immune defenses that could be exploited by S. typhimurium to persist and survive in the host.

Original languageEnglish (US)
Pages (from-to)385-390
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume111
Issue number1
DOIs
StatePublished - 2014

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Salmonella
Infection
Foodborne Diseases
Salmonella enterica
Salmonella Infections
Pyrin Domain
NLR Proteins
Carcinogenesis
Down-Regulation
Nucleotides
Macrophages
Phosphorylation
Inflammation
Serogroup

ASJC Scopus subject areas

  • General

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Salmonella exploits NLRP12-dependent innate immune signaling to suppress host defenses during infection. / Zaki, Md Hasan; Man, Si Ming; Vogel, Peter; Lamkanfi, Mohamed; Kanneganti, Thirumala Devi.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 111, No. 1, 2014, p. 385-390.

Research output: Contribution to journalArticle

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