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Reactive oxygen species regulate caspase-11 expression and activation of the non-canonical NLRP3 inflammasome during enteric pathogen infection

(2014) PLOS PATHOGENS. 10(9).
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Abstract
Enteropathogenic and enterohemorrhagic bacterial infections in humans are a severe cause of morbidity and mortality. Although NOD-like receptors (NLRs) NOD2 and NLRP3 have important roles in the generation of protective immune responses to enteric pathogens, whether there is crosstalk among NLRs to regulate immune signaling is not known. Here, we show that mice and macrophages deficient in NOD2, or the downstream adaptor RIP2, have enhanced NLRP3-and caspases-11-dependent non-canonical inflammasome activation in a mouse model of enteropathogenic Citrobacter rodentium infection. Mechanistically, NOD2 and RIP2 regulate reactive oxygen species (ROS) production. Increased ROS in Rip2-deficient macrophages subsequently enhances c-Jun N-terminal kinase (JNK) signaling resulting in increased caspase-11 expression and activation, and more non-canonical NLRP3-dependant inflammasome activation. Intriguingly, this leads to protection of the colon epithelium for up to 10 days in Rip2-deficient mice infected with C. rodentium. Our findings designate NOD2 and RIP2 as key regulators of cellular ROS homeostasis and demonstrate for the first time that ROS regulates caspase-11 expression and non-canonical NLRP3 inflammasome activation through the JNK pathway.
Keywords
CROHNS-DISEASE, PYROPTOSIS, INDUCED COLITIS, CYTOPLASMIC LPS, EFFACING PATHOGEN, LISTERIA-MONOCYTOGENES, HOST-DEFENSE, CITROBACTER-RODENTIUM INFECTION, NF-KAPPA-B, INNATE

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Chicago
Lupfer, Christopher R, Paras K Anand, Zhiping Liu, Kate L Stokes, Peter Vogel, Mohamed Lamkanfi, and Thirumala-Devi Kanneganti. 2014. “Reactive Oxygen Species Regulate Caspase-11 Expression and Activation of the Non-canonical NLRP3 Inflammasome During Enteric Pathogen Infection.” Plos Pathogens 10 (9).
APA
Lupfer, C. R., Anand, P. K., Liu, Z., Stokes, K. L., Vogel, P., Lamkanfi, M., & Kanneganti, T.-D. (2014). Reactive oxygen species regulate caspase-11 expression and activation of the non-canonical NLRP3 inflammasome during enteric pathogen infection. PLOS PATHOGENS, 10(9).
Vancouver
1.
Lupfer CR, Anand PK, Liu Z, Stokes KL, Vogel P, Lamkanfi M, et al. Reactive oxygen species regulate caspase-11 expression and activation of the non-canonical NLRP3 inflammasome during enteric pathogen infection. PLOS PATHOGENS. 2014;10(9).
MLA
Lupfer, Christopher R et al. “Reactive Oxygen Species Regulate Caspase-11 Expression and Activation of the Non-canonical NLRP3 Inflammasome During Enteric Pathogen Infection.” PLOS PATHOGENS 10.9 (2014): n. pag. Print.
@article{5809998,
  abstract     = {Enteropathogenic and enterohemorrhagic bacterial infections in humans are a severe cause of morbidity and mortality. Although NOD-like receptors (NLRs) NOD2 and NLRP3 have important roles in the generation of protective immune responses to enteric pathogens, whether there is crosstalk among NLRs to regulate immune signaling is not known. Here, we show that mice and macrophages deficient in NOD2, or the downstream adaptor RIP2, have enhanced NLRP3-and caspases-11-dependent non-canonical inflammasome activation in a mouse model of enteropathogenic Citrobacter rodentium infection. Mechanistically, NOD2 and RIP2 regulate reactive oxygen species (ROS) production. Increased ROS in Rip2-deficient macrophages subsequently enhances c-Jun N-terminal kinase (JNK) signaling resulting in increased caspase-11 expression and activation, and more non-canonical NLRP3-dependant inflammasome activation. Intriguingly, this leads to protection of the colon epithelium for up to 10 days in Rip2-deficient mice infected with C. rodentium. Our findings designate NOD2 and RIP2 as key regulators of cellular ROS homeostasis and demonstrate for the first time that ROS regulates caspase-11 expression and non-canonical NLRP3 inflammasome activation through the JNK pathway.},
  articleno    = {e1004410},
  author       = {Lupfer, Christopher R and Anand, Paras K and Liu, Zhiping and Stokes, Kate L and Vogel, Peter and Lamkanfi, Mohamed and Kanneganti, Thirumala-Devi},
  issn         = {1553-7366},
  journal      = {PLOS PATHOGENS},
  keywords     = {CROHNS-DISEASE,PYROPTOSIS,INDUCED COLITIS,CYTOPLASMIC LPS,EFFACING PATHOGEN,LISTERIA-MONOCYTOGENES,HOST-DEFENSE,CITROBACTER-RODENTIUM INFECTION,NF-KAPPA-B,INNATE},
  language     = {eng},
  number       = {9},
  pages        = {14},
  title        = {Reactive oxygen species regulate caspase-11 expression and activation of the non-canonical NLRP3 inflammasome during enteric pathogen infection},
  url          = {http://dx.doi.org/10.1371/journal.ppat.1004410},
  volume       = {10},
  year         = {2014},
}

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