Journal article
DsRNA induces apoptosis through an atypical death complex associating TLR3 to caspase-8
Y Estornes, F Toscano, F Virard, G Jacquemin, A Pierrot, B Vanbervliet, M Bonnin, N Lalaoui, P Mercier-Gouy, Y Pachéco, B Salaun, T Renno, O Micheau, S Lebecque
Cell Death and Differentiation | Published : 2012
DOI: 10.1038/cdd.2012.22
Abstract
Toll-like receptor 3 (TLR3) is a pattern-recognition receptor known to initiate an innate immune response when stimulated by double-stranded RNA (dsRNA). Components of TLR3 signaling, including TIR domain-containing adapter inducing IFN-α (TRIF), have been demonstrated to contribute to dsRNA-induced cell death through caspase-8 and receptor interacting protein (RIP)1 in various human cancer cells. We provide here a detailed analysis of the caspase-8 activating machinery triggered in response to Poly(I:C) dsRNA. Engagement of TLR3 by dsRNA in both type I and type II lung cancer cells induces the formation of an atypical caspase-8-containing complex that is devoid of classical death receptors ..
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Awarded by Agence Nationale de la Recherche
Funding Acknowledgements
We thank our colleagues who provided reagents, especially Patrick Mehlen for the Bcl-2-expressing plasmid, Wayne Fairbrother for the gift of Smac mimetic BV6, Isabelle Grosjean for her assistance with cultures, Stephanie Brunet-Manquat and Isabelle Durand for their support with flow cytometry, Jean-Paul Pais De Barros for assistance with size-exclusion chromatography, and our colleagues in the laboratory for their restless support and encouragement. The Canceropole Lyon Auvergne Rhone-Alpes (CLARA) funded the work and SL was supported by a grant from the Hospices Civils de Lyon. OM was supported by grants from the ANR (Agence Nationale de la Recherche 07-PCV-0031) and the European Community (ApopTrain Marie Curie RTN). GJ and NL were supported by fellowships from the Ligue Nationale contre le Cancer and a joint INSERM and Conseil Regional de Bourgogne fellowship, respectively. We gratefully acknowledge the help and advice of Nicolas Foray.