L’élimination des cellules apoptotiques : une phagocytose particulière

Getting rid of the bodies: a specialized form of phagocytosis

Centre d’Immunologie Inserm-Cnrs de Marseille Luminy, Case 906, Parc Scientifique de Luminy, 13288, Marseille Cedex 09, France

^* chimini@ciml.univ-mrs.fr

Résumé

Le programme de mort cellulaire par apoptose joue un rôle clé dans le maintien de l’homéostasie cellulaire. La première phase du programme conduit au démantèlement de la cellule. Celle-ci est très précocement reconnue et ingérée, par des phagocytes professionnels ou amateurs, grâce à la mise en œuvre d’une phagocytose spécialisée, l’engulfment ou engloutissement. Contrairement à l’attention portée aux mécanismes régissant la phase effectrice de l’apoptose, les bases moléculaires de l’engloutissement de la proie apoptotique ainsi que les conséquences physiologiques pouvant dériver d’une clairance sub-optimale n’ont été étudiées que récemment. Nous nous proposons de discuter ici les dernières avancées du domaine, ainsi que certains des attributs spécifiques de cette forme de phagocytose.

Abstract

Programmed cell death plays a crucial role in the maintenance of cell homeostasis. An initial phase leads to the generation of apoptotic corpses and is closely followed by their clearance by professional or amateur phagocytes. In contrast to the high amount of efforts dedicated to the molecular understanding of the first effector phase, only recently attention has focussed on the downstream engulfment phase. Our aim here is to review and discuss the most recent knowledge of the events ruling this specialized form of phagocytosis. Several aspects distinguish the engulfment of dying cells from the classical forms of phagocytosis targeting foreign microorganism. In this case, in fact, the prey is represented by self cells and the major goal is to clear the corpses swiftly enough to prevent any leakage of intracellular content, potentially dangerous in that it is able to trigger defense responses. In addition, the act of engulfing a dying cell actually induces an active safety control via the upregulation of macrophage anti-inflammatory circuits. Recognising a dying cell among healthy neighbours is a complex matter and several receptors on the phagocyte surface participate in the recognition. Unfortunately, in most cases, how they exactly interact with the apoptotic membrane and/or with each other is still unknown. Two parallel and partially redundant molecular cascades are activated in the phagocyte by the engagement of engulfment receptors. These involve proteins conserved across evolution from C. elegans to mammals. How these pathways however communicate to give rise to the final silencing of immune responses is still elusive.