Viral subversion of immunogenic cell death

Oliver Kepp, Laura Senovilla, Lorenzo Galluzzi, Theocharis Panaretakis, Antoine Tesniere, Frederic Schlemmer, Frank Madeo, Laurence Zitvogel, Guido Kroemer

    Résultats de recherche: Contribution à un journalArticle 'review'Revue par des pairs

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    Résumé

    While physiological cell death is non-immunogenic, pathogen induced cell death can be immunogenic and hence stimulate an immune response against antigens that derive from dying cells and are presented by dendritic cells (DCs). The obligate immunogenic "eat-me" signal generated by dying cells consists in the exposure of calreticulin (CRT) at the cell surface. This particular "eat-me" signal, which facilitates engulfment by DCs, can only be found on cells that succumb to immunogenic apoptosis, while it is not present on cells dying in an immunologically silent fashion. CRT normally resides in the lumen of the endoplasmic reticulum (ER), yet can translocate to the plasma membrane surface through a complex pathway that involves elements of the ER stress response (e.g., the eIF2α-phosphorylating kinase PERK), the apoptotic machinery (e.g., caspase-8 and its substrate BAP31, Bax, Bak), the anterograde transport from the ER to the Golgi apparatus, and SNARE-dependent exocytosis. A large panoply of viruses encodes proteins that inhibit eIF2α kinases, catalyze the dephosphorylation of eIF2α, bind to caspase-8, Bap31, Bax or Bak, or perturb exocytosis. We therefore postulate that obligate intracellular pathogens have developed a variety of strategies to subvert CRT exposure, thereby avoiding immunogenic cell death.

    langue originaleAnglais
    Pages (de - à)860-869
    Nombre de pages10
    journalCell Cycle
    Volume8
    Numéro de publication6
    Les DOIs
    étatPublié - 15 mars 2009

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