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

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 down-regulation 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.
AuthorsMd Hasan Zaki, Si Ming Man, Peter Vogel, Mohamed Lamkanfi, Thirumala-Devi Kanneganti
JournalProceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 111 Issue 1 Pg. 385-90 (Jan 07 2014) ISSN: 1091-6490 [Electronic] United States
PMID24347638 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Intracellular Signaling Peptides and Proteins
  • NF-kappa B
  • NLRP12 protein, mouse
  • Nucleotides
  • Nitric Oxide
  • Extracellular Signal-Regulated MAP Kinases
Topics
  • Animals
  • Bone Marrow Cells (immunology, microbiology)
  • Extracellular Signal-Regulated MAP Kinases (metabolism)
  • Host-Pathogen Interactions
  • Immunity, Innate
  • Inflammation
  • Intracellular Signaling Peptides and Proteins (metabolism)
  • Liver (metabolism)
  • Macrophages (microbiology)
  • Male
  • Mice
  • Mice, Transgenic
  • Models, Biological
  • NF-kappa B (metabolism)
  • Nitric Oxide (chemistry)
  • Nucleotides (chemistry)
  • Protein Structure, Tertiary
  • Salmonella Infections, Animal (immunology, microbiology)
  • Salmonella typhimurium (metabolism)
  • Signal Transduction
  • Time Factors

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