Details

Autor(en) / Beteiligte

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

Titel

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

Ist Teil von

• The Journal of immunology (1950), 2014-02, Vol.192 (4), p.1835-1846

Ort / Verlag

United States

Erscheinungsjahr

2014

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.