Toll or Interleukin-1 Receptor (TIR) Domain-containing Adaptor Inducing Interferon-β (TRIF)-mediated Caspase-11 Protease Production Integrates Toll-like Receptor 4 (TLR4) Protein- and Nlrp3 Inflammasome-mediated Host Defense against Enteropathogens

Prajwal Gurung; R. K.Subbarao Malireddi; Paras K Anand; Dieter Demon; Lieselotte Vande Walle; Zhiping Liu; Peter Vogel; Mohamed Lamkanfi; Thirumala-Devi Kanneganti

doi:10.1074/jbc.M112.401406

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Toll or Interleukin-1 Receptor (TIR) Domain-containing Adaptor Inducing Interferon-β (TRIF)-mediated Caspase-11 Protease Production Integrates Toll-like Receptor 4 (TLR4) Protein- and Nlrp3 Inflammasome-mediated Host Defense against Enteropathogens

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Toll or Interleukin-1 Receptor (TIR) Domain-containing Adaptor Inducing Interferon-β (TRIF)-mediated Caspase-11 Protease Production Integrates Toll-like Receptor 4 (TLR4) Protein- and Nlrp3 Inflammasome-mediated Host Defense against Enteropathogens

Prajwal Gurung, R. K.Subbarao Malireddi, Paras K Anand, Dieter Demon, Lieselotte Vande Walle, Zhiping Liu, Peter Vogel, Mohamed Lamkanfi and Thirumala-Devi Kanneganti

The Journal of biological chemistry, Vol.287(41), pp.34474-34483

10/05/2012

DOI: 10.1074/jbc.M112.401406

PMCID: PMC3464552

PMID: 22898816

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Abstract

Enteric pathogens represent a major cause of morbidity and mortality worldwide. Toll-like receptor (TLR) and inflammasome signaling are critical for host responses against these pathogens, but how these pathways are integrated remains unclear. Here, we show that TLR4 and the TLR adaptor TRIF are required for inflammasome activation in macrophages infected with the enteric pathogens Escherichia coli and Citrobacter rodentium. In contrast, TLR4 and TRIF were dispensable for Salmonella typhimurium-induced caspase-1 activation. TRIF regulated expression of caspase-11, a caspase-1-related protease that is critical for E. coli- and C. rodentium-induced inflammasome activation, but dispensable for inflammasome activation by S. typhimurium. Thus, TLR4- and TRIF-induced caspase-11 synthesis is critical for noncanonical Nlrp3 inflammasome activation in macrophages infected with enteric pathogens. Background:C. rodentium and E. coli induce noncanonical Nlrp3 inflammasome activation through caspase-11. Results: TLR4-TRIF are important for caspase-11 expression, caspase-1 activation, and downstream IL-1β and IL-18 production. Conclusion: TLR4-TRIF axis plays an important role in the up-regulation of caspase-11 and activation of noncanonical inflammasome. Significance: Our study identifies novel molecules upstream of caspase-11 that are involved in activation of noncanonical inflammasome.

Noncanonical Inflammasome

Immunology

Toll-like receptor (TLR)

Caspase-11

Nod-like receptor (NLR)

Innate Immunity

Caspase

TRIF

TLR4

Caspase-1

Details

Title: Subtitle: Toll or Interleukin-1 Receptor (TIR) Domain-containing Adaptor Inducing Interferon-β (TRIF)-mediated Caspase-11 Protease Production Integrates Toll-like Receptor 4 (TLR4) Protein- and Nlrp3 Inflammasome-mediated Host Defense against Enteropathogens
Creators: Prajwal Gurung - Department of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105
R. K.Subbarao Malireddi - Department of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105
Paras K Anand - Department of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105
Dieter Demon - Department of Biochemistry, VIB, Ghent University, B-9000 Ghent, Belgium
Lieselotte Vande Walle - Department of Biochemistry, VIB, Ghent University, B-9000 Ghent, Belgium
Zhiping Liu - Department of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105
Peter Vogel - Animal Resources Center and the Veterinary Pathology Core, St. Jude Children's Research Hospital, Memphis, Tennessee 38105
Mohamed Lamkanfi - Department of Biochemistry, VIB, Ghent University, B-9000 Ghent, Belgium
Thirumala-Devi Kanneganti - Department of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105
Resource Type: Journal article
Publication Details: The Journal of biological chemistry, Vol.287(41), pp.34474-34483
DOI: 10.1074/jbc.M112.401406
PMID: 22898816
PMCID: PMC3464552
NLM abbreviation: J Biol Chem
ISSN: 0021-9258
eISSN: 1083-351X
Publisher: Elsevier Inc
Language: English
Date published: 10/05/2012
Academic Unit: Infectious Diseases; Internal Medicine
Record Identifier: 9984094343202771

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