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.
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Authors | Md Hasan Zaki, Si Ming Man, Peter Vogel, Mohamed Lamkanfi, Thirumala-Devi Kanneganti |
Journal | Proceedings 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 |
PMID | 24347638
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Intracellular Signaling Peptides and Proteins
- NF-kappa B
- NLRP12 protein, mouse
- Nucleotides
- Nitric Oxide
- Extracellular Signal-Regulated MAP Kinases
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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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