Targeting apoptosis pathways in infections

J Leukoc Biol. 2018 Feb;103(2):275-285. doi: 10.1189/JLB.4MR0717-286R.

Abstract

The programmed cell death pathway of apoptosis is essential for mammalian development and immunity as it eliminates unwanted and dangerous cells. As part of the cellular immune response, apoptosis removes the replicative niche of intracellular pathogens and enables the resolution of infections. To subvert apoptosis, pathogens have evolved a diverse range of mechanisms. In some circumstances, however, pathogens express effector molecules that induce apoptotic cell death. In this review, we focus on selected host-pathogen interactions that affect apoptotic pathways. We discuss how pathogens control the fate of host cells and how this determines the outcome of infections. Finally, small molecule inhibitors that activate apoptosis in cancer cells can also induce apoptotic cell death of infected cells. This suggests that targeting host death factors to kill infected cells is a potential therapeutic option to treat infectious diseases.

Keywords: BCL-2; Legionella; caspase; cell death; inflammation; mitochondria.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Apoptosis Regulatory Proteins / metabolism
  • Communicable Diseases / drug therapy*
  • Disease Models, Animal
  • Host-Pathogen Interactions*
  • Humans
  • Immune System / physiology
  • Mice, Knockout
  • Mitochondria / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / metabolism

Substances

  • Apoptosis Regulatory Proteins
  • Proto-Oncogene Proteins c-bcl-2