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

Prajwal Gurung; Paras K Anand; R K Subbarao Malireddi; Lieselotte Vande Walle; Nina Van Opdenbosch; Christopher P Dillon; Ricardo Weinlich; Douglas R Green; Mohamed Lamkanfi; Thirumala-Devi Kanneganti

doi:10.4049/jimmunol.1302839

Back

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

Journal article

Peer reviewed

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

Prajwal Gurung, Paras K Anand, R K Subbarao Malireddi, Lieselotte Vande Walle, Nina Van Opdenbosch, Christopher P Dillon, Ricardo Weinlich, Douglas R Green, Mohamed Lamkanfi and Thirumala-Devi Kanneganti

The Journal of immunology (1950), Vol.192(4), pp.1835-1846

02/15/2014

DOI: 10.4049/jimmunol.1302839

PMCID: PMC3933570

PMID: 24453255

View Online

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-1β 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.

Calcium-Binding Proteins - metabolism

Fas-Associated Death Domain Protein - genetics

Citrobacter rodentium - immunology

NLR Family, Pyrin Domain-Containing 3 Protein

Caspase 8 - metabolism

Fas-Associated Death Domain Protein - metabolism

Caspase 1 - metabolism

Apoptosis Regulatory Proteins - metabolism

Lipopolysaccharides

Mice, Knockout

Caspase 8 - genetics

Enterobacteriaceae Infections - immunology

Caspase 8 - immunology

Receptor-Interacting Protein Serine-Threonine Kinases - genetics

Animals

Caspases - metabolism

Interleukin-1beta - metabolism

Inflammasomes - immunology

Transcription, Genetic

Mice

Receptor-Interacting Protein Serine-Threonine Kinases - deficiency

Enzyme Activation

Carrier Proteins - immunology

Macrophages - immunology

Details

Title: Subtitle: FADD and caspase-8 mediate priming and activation of the canonical and noncanonical Nlrp3 inflammasomes
Creators: Prajwal Gurung - Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105
Paras K Anand
R K Subbarao Malireddi
Lieselotte Vande Walle
Nina Van Opdenbosch
Christopher P Dillon
Ricardo Weinlich
Douglas R Green
Mohamed Lamkanfi
Thirumala-Devi Kanneganti
Resource Type: Journal article
Publication Details: The Journal of immunology (1950), Vol.192(4), pp.1835-1846
DOI: 10.4049/jimmunol.1302839
PMID: 24453255
PMCID: PMC3933570
NLM abbreviation: J Immunol
ISSN: 0022-1767
eISSN: 1550-6606
Grant note: R01 AI101935 / NIAID NIH HHS R01 AI044828 / NIAID NIH HHS 281600 / European Research Council R01 CA163507 / NCI NIH HHS R01 CA169291 / NCI NIH HHS P30 CA021765 / NCI NIH HHS R01 AR056296 / NIAMS NIH HHS AI101935 / NIAID NIH HHS R37 AI101935 / NIAID NIH HHS CA163507 / NCI NIH HHS AR056296 / NIAMS NIH HHS
Language: English
Date published: 02/15/2014
Academic Unit: Infectious Diseases; Internal Medicine
Record Identifier: 9984094360402771

Metrics

22 Record Views

476 Times Cited - Web of Science

See more details