Autophagy in infection.
Autophagy is a ubiquitous eukaryotic cytoplasmic quality and quantity control pathway. The role of autophagy in cytoplasmic homeostasis seamlessly extends to cell-autonomous defense against intracellular microbes. Recent studies also point to fully integrated, multitiered regulatory and effector connections between autophagy and nearly all facets of innate and adaptive immunity. Autophagy in the immune system as a whole confers measured immune responses; on the flip side, suppression of autophagy can lead to inflammation and tissue damage, as evidenced by Crohn's disease predisposition polymorphisms in autophagy basal apparatus (Atg16L) and regulatory (IRGM) genes. Polymorphisms in the IRGM gene in human populations have also been linked to predisposition to tuberculosis. There are several areas of most recent growth: first, links between autophagy regulators and infectious disease predisposition in human populations; second, demonstration of a role for autophagy in infection control in vivo in animal models; third, the definition of specific antiautophagic defenses in highly evolved pathogens; and fourth, recognition of connections between the ubiquitin system and autophagy of bacteria (and interestingly mitochondria, which are incidentally organelles of bacterial evolutionary origin) via a growing list of modifier and adapter proteins including p62/SQSTM1, NDP52, Atg32, Parkin, and Nix/BNIP3L.
Deretic
Vojo
V
Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, 915 Camino de Salud NE, Albuquerque, NM 87131, USA. vderetic@salud.unm.edu
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D001343:Autophagy; D006801:Humans; D007109:Immunity / Q000276:immunology; D007239:Infections / Q000276:immunology / Q000473:pathology*; D008928:Mitochondria / Q000378:metabolism; D023421:Models, Animal
D048868:Adaptor Proteins, Signal Transducing