Autophagy and checkpoints for intracellular pathogen defense.
OBJECTIVE
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.


RESULTS
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.


CONCLUSIONS
Autophagy-dependent and autophagy-related gene-dependent pathways are essential in intracellular defense against a broad range of pathogens.
aBroad Institute of Harvard University and Massachusetts Institute of Technology, Cambridge bGastrointestinal Unit, Center for the Study of Inflammatory Bowel Disease, and Center for Computational and Integrative Biology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Geraldine L C
GL
Paulus
Ramnik J
RJ
Xavier
D000818:Animals; D001343:Autophagy / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular / Q000235:genetics / Q000276:immunology; D007239:Infections / Q000235:genetics / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology; D008869:Microtubule-Associated Proteins / Q000276:immunology; D010587:Phagocytosis / Q000276:immunology; D014123:Toxoplasmosis / Q000235:genetics / Q000276:immunology
C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins; D007371:Interferon-gamma