Universität zu Köln

Herb, Marc ORCID: 0000-0002-7533-0288, Gluschko, Alexander ORCID: 0000-0002-1090-1756, Farid, Alina and Kroenke, Martin (2022). When the Phagosome Gets Leaky: Pore-Forming Toxin-Induced Non-Canonical Autophagy (PINCA). Front. Cell. Infect. Microbiol., 12. LAUSANNE: FRONTIERS MEDIA SA. ISSN 2235-2988

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Abstract

Macrophages remove bacteria from the extracellular milieu via phagocytosis. While most of the engulfed bacteria are degraded in the antimicrobial environment of the phagolysosome, several bacterial pathogens have evolved virulence factors, which evade degradation or allow escape into the cytosol. To counter this situation, macrophages activate LC3-associated phagocytosis (LAP), a highly bactericidal non-canonical autophagy pathway, which destroys the bacterial pathogens in so called LAPosomes. Moreover, macrophages can also target intracellular bacteria by pore-forming toxin-induced non-canonical autophagy (PINCA), a recently described non-canonical autophagy pathway, which is activated by phagosomal damage induced by bacteria-derived pore-forming toxins. Similar to LAP, PINCA involves LC3 recruitment to the bacteria-containing phagosome independently of the ULK complex, but in contrast to LAP, this process does not require ROS production by Nox2. As last resort of autophagic targeting, macrophages activate xenophagy, a selective form of macroautophagy, to recapture bacteria, which evaded successful targeting by LAP or PINCA through rupture of the phagosome. However, xenophagy can also be hijacked by bacterial pathogens for their benefit or can be completely inhibited resulting in intracellular growth of the bacterial pathogen. In this perspective, we discuss the molecular differences and similarities between LAP, PINCA and xenophagy in macrophages during bacterial infections.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Herb, Marc UNSPECIFIED orcid.org/0000-0002-7533-0288 UNSPECIFIED Gluschko, Alexander UNSPECIFIED orcid.org/0000-0002-1090-1756 UNSPECIFIED Farid, Alina UNSPECIFIED UNSPECIFIED UNSPECIFIED Kroenke, Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-670783
DOI:	10.3389/fcimb.2022.834321
Journal or Publication Title:	Front. Cell. Infect. Microbiol.
Volume:	12
Date:	2022
Publisher:	FRONTIERS MEDIA SA
Place of Publication:	LAUSANNE
ISSN:	2235-2988
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CHAIN 3 PROTEIN; LC3-ASSOCIATED PHAGOCYTOSIS; NADPH OXIDASE; MYCOBACTERIUM-TUBERCULOSIS; ATG12-ATG5 CONJUGATE; APOPTOTIC CELLS; CUTTING EDGE; ATG PROTEINS; SALMONELLA; COMPLEX Multiple languages Immunology; Microbiology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/67078