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Autophagy and checkpoints for intracellular pathogen defense

Paulus, Geraldine L.C.a,b; Xavier, Ramnik J.a,b

Current Opinion in Gastroenterology: January 2015 - Volume 31 - Issue 1 - p 14–23
doi: 10.1097/MOG.0000000000000134
GASTROINTESTINAL INFECTIONS: Edited by Mitchell B. Cohen
Editor's Choice

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.

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

Correspondence to Ramnik J. Xavier, Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital, Richard B. Simches Research Center, 185 Cambridge Street, Boston, MA 02114, USA. Tel: +1 617 643 3331; fax: +1 617 643 3328; e-mail: xavier@molbio.mgh.harvard.edu

© 2015 Wolters Kluwer Health | Lippincott Williams & Wilkins