Detection of a vita-PAMP STINGs cells into reticulophagy

Autophagy
Julien Moretti, J Magarian Blander

Abstract

Phagocytes cope with the threat of living bacteria via detection of vita-PAMPs, a specific class of pathogen-associated molecular patterns (PAMPs) that denotes microbial viability and trigger a commensurate innate response. Prokaryotic mRNA and cyclic-di-adenosine monophosphate (c-di-AMP) serve as vita-PAMPs for Gram-negative and Gram-positive bacteria, respectively, and elicit heightened proinflammatory responses not warranted for dead bacteria. The innate sensor TMEM173/STING detects c-di-AMP produced by internalized live Gram-positive bacteria, and quickly mobilizes interdependent pre-formed cell-autonomous responses including endoplasmic reticulum (ER) stress, MTOR inactivation, and reticulophagy. In turn, reticulophagy serves a dual role in restoring phagocyte homeostasis and orchestrating a type I IFN response. ER-stress induced macroautophagy/autophagy sequesters stressed ER, resolves ER stress and prevents apoptosis in response to live bacteria. Reticulophagy relocalizes ER-resident TMEM173/STING to phagophores, which then act as TMEM173/STING-signaling compartments. Here, we discuss our findings in the context of innate immunity and cell homeostasis.

Citations

Mar 14, 2019·Immunologic Research·Feng SunWenxian Guan
Aug 4, 2018·Frontiers in Pediatrics·Simone S SchüllerOfer Levy
Jul 25, 2019·Frontiers in Cellular and Infection Microbiology·Klara Kubelkova, Ales Macela
Nov 17, 2020·Frontiers in Cellular and Infection Microbiology·Thomas E WoodAbderrahman Hachani

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Methods Mentioned

BETA
protein folding

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