Clearance of dying cells by phagocytes: Mechanisms and implications for disease pathogenesis

Aaron M. Fond, Kodi S. Ravichandran

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review

41 Scopus citations

Abstract

The efficient clearance of apoptotic cells is an evolutionarily conserved process crucial for homeostasis in multicellular organisms. The clearance involves a series of steps that ultimately facilitates the recognition of the apoptotic cell by the phagocytes and the subsequent uptake and processing of the corpse. These steps include the phagocyte sensing of "find-me" signals released by the apoptotic cell, recognizing "eat-me" signals displayed on the apoptotic cell surface, and then intracellular signaling within the phagocyte to mediate phagocytic cup formation around the corpse and corpse internalization, and the processing of the ingested contents. The engulfment of apoptotic cells by phagocytes not only eliminates debris from tissues but also produces an anti-inflammatory response that suppresses local tissue inflammation. Conversely, impaired corpse clearance can result in loss of immune tolerance and the development of various inflammation-associated disorders such as autoimmunity, atherosclerosis, and airway inflammation but can also affect cancer progression. Recent studies suggest that the clearance process can also influence antitumor immune responses. In this review, we will discuss how apoptotic cells interact with their engulfing phagocytes to generate important immune responses, and how modulation of such responses can influence pathology.

Original languageEnglish
Title of host publicationAdvances in Experimental Medicine and Biology
PublisherSpringer New York LLC
Pages25-49
Number of pages25
DOIs
StatePublished - 2016

Publication series

NameAdvances in Experimental Medicine and Biology
Volume930
ISSN (Print)0065-2598
ISSN (Electronic)2214-8019

Keywords

  • Apoptosis
  • Cancer
  • Cell clearance
  • Engulfment
  • Immune tolerance

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