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FADD and Caspase-8 mediate priming and activation of the canonical and noncanonical Nlrp3 inflammasomes

(2014) JOURNAL OF IMMUNOLOGY. 192(4). p.1835-1846
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Abstract
The Nlrp3 inflammasome is critical for host immunity, but the mechanisms controlling its activation are enigmatic. In this study, we show that loss of FADD or caspase-8 in a RIP3-deficient background, but not RIP3 deficiency alone, hampered transcriptional priming and posttranslational activation of the canonical and noncanonical Nlrp3 inflammasome. Deletion of caspase-8 in the presence or absence of RIP3 inhibited caspase-1 and caspase-11 activation by Nlrp3 stimuli but not the Nlrc4 inflammasome. In addition, FADD deletion prevented caspase-8 maturation, positioning FADD upstream of caspase-8. Consequently, FADD- and caspase-8-deficient mice had impaired IL-1 beta production when challenged with LPS or infected with the enteropathogen Citrobacter rodentium. Thus, our results reveal FADD and caspase-8 as apical mediators of canonical and noncanonical Nlrp3 inflammasome priming and activation.
Keywords
IL-1-BETA, RECEPTORS, B-CELL, IMMUNE-RESPONSE, SIGNALING PATHWAY, TARGETED DISRUPTION, CELL-DEATH, HOST-DEFENSE, SALMONELLA INFECTION, RECEPTORS, CUTTING EDGE

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Chicago
Gurung, Prajwal, Paras K Anand, RK Subbarao Malireddi, Lieselotte Vande Walle, Nina Van Opdenbosch, Christopher P Dillon, Ricardo Weinlich, Douglas R Green, Mohamed Lamkanfi, and Thirumala-Devi Kanneganti. 2014. “FADD and Caspase-8 Mediate Priming and Activation of the Canonical and Noncanonical Nlrp3 Inflammasomes.” Journal of Immunology 192 (4): 1835–1846.
APA
Gurung, P., Anand, P. K., Malireddi, R. S., Vande Walle, L., Van Opdenbosch, N., Dillon, C. P., Weinlich, R., et al. (2014). FADD and Caspase-8 mediate priming and activation of the canonical and noncanonical Nlrp3 inflammasomes. JOURNAL OF IMMUNOLOGY, 192(4), 1835–1846.
Vancouver
1.
Gurung P, Anand PK, Malireddi RS, Vande Walle L, Van Opdenbosch N, Dillon CP, et al. FADD and Caspase-8 mediate priming and activation of the canonical and noncanonical Nlrp3 inflammasomes. JOURNAL OF IMMUNOLOGY. 2014;192(4):1835–46.
MLA
Gurung, Prajwal, Paras K Anand, RK Subbarao Malireddi, et al. “FADD and Caspase-8 Mediate Priming and Activation of the Canonical and Noncanonical Nlrp3 Inflammasomes.” JOURNAL OF IMMUNOLOGY 192.4 (2014): 1835–1846. Print.
@article{4349465,
  abstract     = {The Nlrp3 inflammasome is critical for host immunity, but the mechanisms controlling its activation are enigmatic. In this study, we show that loss of FADD or caspase-8 in a RIP3-deficient background, but not RIP3 deficiency alone, hampered transcriptional priming and posttranslational activation of the canonical and noncanonical Nlrp3 inflammasome. Deletion of caspase-8 in the presence or absence of RIP3 inhibited caspase-1 and caspase-11 activation by Nlrp3 stimuli but not the Nlrc4 inflammasome. In addition, FADD deletion prevented caspase-8 maturation, positioning FADD upstream of caspase-8. Consequently, FADD- and caspase-8-deficient mice had impaired IL-1 beta production when challenged with LPS or infected with the enteropathogen Citrobacter rodentium. Thus, our results reveal FADD and caspase-8 as apical mediators of canonical and noncanonical Nlrp3 inflammasome priming and activation.},
  author       = {Gurung, Prajwal and Anand, Paras K and Malireddi, RK Subbarao and Vande Walle, Lieselotte and Van Opdenbosch, Nina and Dillon, Christopher P and Weinlich, Ricardo and Green, Douglas R and Lamkanfi, Mohamed and Kanneganti, Thirumala-Devi},
  issn         = {0022-1767},
  journal      = {JOURNAL OF IMMUNOLOGY},
  keywords     = {IL-1-BETA,RECEPTORS,B-CELL,IMMUNE-RESPONSE,SIGNALING PATHWAY,TARGETED DISRUPTION,CELL-DEATH,HOST-DEFENSE,SALMONELLA INFECTION,RECEPTORS,CUTTING EDGE},
  language     = {eng},
  number       = {4},
  pages        = {1835--1846},
  title        = {FADD and Caspase-8 mediate priming and activation of the canonical and noncanonical Nlrp3 inflammasomes},
  url          = {http://dx.doi.org/10.4049/jimmunol.1302839},
  volume       = {192},
  year         = {2014},
}

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