Autophagy and checkpoints for intracellular pathogen defense

Curr Opin Gastroenterol. 2015 Jan;31(1):14-23. doi: 10.1097/MOG.0000000000000134.

Abstract

Purpose of review: Autophagy plays a crucial role in intracellular defense against various pathogens. Xenophagy is a form of selective autophagy that targets intracellular pathogens for degradation. In addition, several related, yet distinct, intracellular defense responses depend on autophagy-related genes. This review gives an overview of these processes, pathogen strategies to subvert them, and their crosstalk with various cell death programs.

Recent findings: The recruitment of autophagy-related proteins plays a key role in multiple intracellular defense programs, specifically xenophagy, microtubule-associated protein 1 light chain 3 alpha (LC3)-associated phagocytosis, and the interferon gamma-mediated elimination of pathogens, such as Toxoplasma gondii and murine norovirus. Recent progress has revealed methods employed by pathogens to resist these intracellular defense mechanisms and/or persist in spite of them. The intracellular pathogen load can tip the balance between cell survival and cell death. Further, it was recently observed that LC3-associated phagocytosis is indispensable for the efficient clearance of dying cells.

Summary: Autophagy-dependent and autophagy-related gene-dependent pathways are essential in intracellular defense against a broad range of pathogens.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Autophagy / genetics
  • Autophagy / immunology*
  • Humans
  • Immunity, Cellular / genetics
  • Immunity, Cellular / immunology
  • Infections / genetics
  • Infections / immunology*
  • Interferon-gamma / immunology
  • Microtubule-Associated Proteins / immunology
  • Phagocytosis / immunology
  • Toxoplasmosis / genetics
  • Toxoplasmosis / immunology

Substances

  • MAP1LC3A protein, human
  • Microtubule-Associated Proteins
  • Interferon-gamma