Immunologic manifestations of autophagy
Vojo Deretic, … , Santosh Chauhan, Michael Mandell
Vojo Deretic, … , Santosh Chauhan, Michael Mandell
Published January 2, 2015
Citation Information: J Clin Invest. 2015;125(1):75-84. https://doi.org/10.1172/JCI73945.
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Review

Immunologic manifestations of autophagy

Abstract

The broad immunologic roles of autophagy span innate and adaptive immunity and are often manifested in inflammatory diseases. The immune effects of autophagy partially overlap with its roles in metabolism and cytoplasmic quality control but typically expand further afield to encompass unique immunologic adaptations. One of the best-appreciated manifestations of autophagy is protection against microbial invasion, but this is by no means limited to direct elimination of intracellular pathogens and includes a stratified array of nearly all principal immunologic processes. This Review summarizes the broad immunologic roles of autophagy. Furthermore, it uses the autophagic control of Mycobacterium tuberculosis as a paradigm to illustrate the breadth and complexity of the immune effects of autophagy.

Authors

Vojo Deretic, Tomonori Kimura, Graham Timmins, Pope Moseley, Santosh Chauhan, Michael Mandell

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Figure 1

Autophagy modulates inflammation.

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Autophagy modulates inflammation. (A) Autophagy — a simplified pathway. ...
(A) Autophagy — a simplified pathway. TOR, AMPK, and immune signaling control activation of ULK1 and beclin 1, the central regulators of autophagy, which in turn bring about autophagic membrane formation (crescent represents a nascent phagophore) from ER with contributions from endosomes and lipid droplets (LD). Completed autophagosomes (double membrane) fuse with lysosomes to form autolysosomes or autophagolysosomes, as described in the text. (B) Autophagy promotes delivery of PAMPs and activation of endosomal TLRs (TLR7 and TLR9) and assists the unconventional secretion of IL-1β upon inflammasome activation. (C) Autophagy inhibits spurious or excessive inflammasome activation and interferes (directly or indirectly) with signaling via cGAS (generating cGAMP upon dsDNA binding), MAVS, and RIG-I to downregulate type I IFN responses, and can suppress NF-κB activation.