Gluschko, Alexander ORCID: 0000-0002-1090-1756, Farid, Alina, Herb, Marc ORCID: 0000-0002-7533-0288, Grumme, Daniela, Kroenke, Martin and Schramm, Michael . Macrophages target Listeria monocytogenes by two discrete non-canonical autophagy pathways. Autophagy. PHILADELPHIA: TAYLOR & FRANCIS INC. ISSN 1554-8635

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Abstract

Non-canonical autophagy pathways decorate single-membrane vesicles with Atg8-family proteins such as MAP1LC3/LC3 (microtubule-associated protein 1 light chain 3). Phagosomes containing the bacterial pathogen Listeria monocytogenes (L.m.) can be targeted by a non-canonical autophagy pathway called LC3-associated phagocytosis (LAP), which substantially contributes to the anti-listerial activity of macrophages and immunity. We here characterized a second non-canonical autophagy pathway targeting L.m.-containing phagosomes, which is induced by damage caused to the phagosomal membrane by the pore-forming toxin of L.m., listeriolysin O. This pore-forming toxin-induced non-canonical autophagy pathway (PINCA) was the only autophagic pathway evoked in tissue macrophages deficient for the NADPH oxidase CYBB/NOX2 that produces the reactive oxygen species (ROS) that are required for LAP induction. Similarly, also bone marrow-derived macrophages (BMDM) exclusively targeted L.m. by PINCA as they completely failed to induce LAP because of insufficient production of ROS through CYBB, in part, due to low expression of some CYBB complex subunits. Priming of BMDM with proinflammatory cytokines such as TNF and IFNG/IFN gamma increased ROS production by CYBB and endowed them with the ability to target L.m. by LAP. Targeting of L.m. by LAP remained relatively rare, though, preventing LAP from substantially contributing to the anti-listerial activity of BMDM. Similar to LAP, the targeting of L.m.-containing phagosomes by PINCA promoted their fusion with lysosomes. Surprisingly, however, this did not substantially contribute to anti-listerial activity of BMDM. Thus, in contrast to LAP, PINCA does not have clear anti-listerial function suggesting that the two different non-canonical autophagy pathways targeting L.m. may have discrete functions.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Gluschko, AlexanderUNSPECIFIEDorcid.org/0000-0002-1090-1756UNSPECIFIED
Farid, AlinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Herb, MarcUNSPECIFIEDorcid.org/0000-0002-7533-0288UNSPECIFIED
Grumme, DanielaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kroenke, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schramm, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-577955
DOI: 10.1080/15548627.2021.1969765
Journal or Publication Title: Autophagy
Publisher: TAYLOR & FRANCIS INC
Place of Publication: PHILADELPHIA
ISSN: 1554-8635
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
LC3-ASSOCIATED PHAGOCYTOSIS; ANTIBACTERIAL AUTOPHAGY; HOST; MECHANISMS; INFECTION; PROTEINS; GLYCANS; GROWTH; DAMAGE; ACTAMultiple languages
Cell BiologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/57795

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