Control of infection by LC3-associated phagocytosis, CASM, and detection of raised vacuolar pH by the V-ATPase-ATG16L1 axis



Wang, Yingxue, Ramos, Maria, Jefferson, Matthew, Zhang, Weijiao, Beraza, Naiara, Carding, Simon, Powell, Penny P, Stewart, James P ORCID: 0000-0002-8928-2037, Mayer, Ulrike and Wileman, Thomas
(2022) Control of infection by LC3-associated phagocytosis, CASM, and detection of raised vacuolar pH by the V-ATPase-ATG16L1 axis. SCIENCE ADVANCES, 8 (43). eabn3298-.

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Abstract

The delivery of pathogens to lysosomes for degradation provides an important defense against infection. Degradation is enhanced when LC3 is conjugated to endosomes and phagosomes containing pathogens to facilitate fusion with lysosomes. In phagocytic cells, TLR signaling and Rubicon activate LC3-associated phagocytosis (LAP) where stabilization of the NADPH oxidase leads to sustained ROS production and raised vacuolar pH. Raised pH triggers the assembly of the vacuolar ATPase on the vacuole membrane where it binds ATG16L1 to recruit the core LC3 conjugation complex (ATG16L1:ATG5-12). This V-ATPase-ATG16L1 axis is also activated in nonphagocytic cells to conjugate LC3 to endosomes containing extracellular microbes. Pathogens provide additional signals for recruitment of LC3 when they raise vacuolar pH with pore-forming toxins and proteins, phospholipases, or specialized secretion systems. Many microbes secrete virulence factors to inhibit ROS production and/or the V-ATPase-ATG16L1 axis to slow LC3 recruitment and avoid degradation in lysosomes.

Item Type: Article
Uncontrolled Keywords: Infectious Diseases, Vaccine Related, Prevention
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Infection, Veterinary and Ecological Sciences
Depositing User: Symplectic Admin
Date Deposited: 25 Jan 2023 12:33
Last Modified: 15 Mar 2024 03:53
DOI: 10.1126/sciadv.abn3298
Open Access URL: https://doi.org/10.1126/sciadv.abn3298
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3167882