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

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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-kappa B and ERK activation by suppressing phosphorylation of I kappa B alpha 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.
Keywords
PROTEIN, RECOGNITION, ACTIVATION, COLON INFLAMMATION, INFLAMMASOME RECEPTORS, BACTERIAL PEPTIDOGLYCAN, MACROPHAGES, TUMORIGENESIS, PATHWAYS, NF-KAPPA-B

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Citation

Please use this url to cite or link to this publication:

Chicago
Zaki, Md Hasan, Si Ming Man, Peter Vogel, Mohamed Lamkanfi, and Thirumala-Devi Kanneganti. 2014. “Salmonella Exploits NLRP12-dependent Innate Immune Signaling to Suppress Host Defenses During Infection.” Proceedings of the National Academy of Sciences of the United States of America 111 (1): 385–390.
APA
Zaki, Md Hasan, Man, S. M., Vogel, P., Lamkanfi, M., & Kanneganti, T.-D. (2014). Salmonella exploits NLRP12-dependent innate immune signaling to suppress host defenses during infection. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 111(1), 385–390.
Vancouver
1.
Zaki MH, Man SM, Vogel P, Lamkanfi M, Kanneganti T-D. Salmonella exploits NLRP12-dependent innate immune signaling to suppress host defenses during infection. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. 2014;111(1):385–90.
MLA
Zaki, Md Hasan, Si Ming Man, Peter Vogel, et al. “Salmonella Exploits NLRP12-dependent Innate Immune Signaling to Suppress Host Defenses During Infection.” PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 111.1 (2014): 385–390. Print.
@article{4307440,
  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-kappa B and ERK activation by suppressing phosphorylation of I kappa B alpha 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.},
  author       = {Zaki, Md Hasan and Man, Si Ming and Vogel, Peter and Lamkanfi, Mohamed and Kanneganti, Thirumala-Devi},
  issn         = {0027-8424},
  journal      = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA},
  keywords     = {PROTEIN,RECOGNITION,ACTIVATION,COLON INFLAMMATION,INFLAMMASOME RECEPTORS,BACTERIAL PEPTIDOGLYCAN,MACROPHAGES,TUMORIGENESIS,PATHWAYS,NF-KAPPA-B},
  language     = {eng},
  number       = {1},
  pages        = {385--390},
  title        = {Salmonella exploits NLRP12-dependent innate immune signaling to suppress host defenses during infection},
  url          = {http://dx.doi.org/10.1073/pnas.1317643111},
  volume       = {111},
  year         = {2014},
}

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