Cargando…

When the Phagosome Gets Leaky: Pore-Forming Toxin-Induced Non-Canonical Autophagy (PINCA)

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Herb, Marc, Gluschko, Alexander, Farid, Alina, Krönke, Martin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8968195/
https://www.ncbi.nlm.nih.gov/pubmed/35372127
http://dx.doi.org/10.3389/fcimb.2022.834321
_version_ 1784678997513207808
author Herb, Marc
Gluschko, Alexander
Farid, Alina
Krönke, Martin
author_facet Herb, Marc
Gluschko, Alexander
Farid, Alina
Krönke, Martin
author_sort Herb, Marc
collection PubMed
description 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.
format Online
Article
Text
id pubmed-8968195
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-89681952022-04-01 When the Phagosome Gets Leaky: Pore-Forming Toxin-Induced Non-Canonical Autophagy (PINCA) Herb, Marc Gluschko, Alexander Farid, Alina Krönke, Martin Front Cell Infect Microbiol Cellular and Infection Microbiology 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. Frontiers Media S.A. 2022-03-17 /pmc/articles/PMC8968195/ /pubmed/35372127 http://dx.doi.org/10.3389/fcimb.2022.834321 Text en Copyright © 2022 Herb, Gluschko, Farid and Krönke https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cellular and Infection Microbiology
Herb, Marc
Gluschko, Alexander
Farid, Alina
Krönke, Martin
When the Phagosome Gets Leaky: Pore-Forming Toxin-Induced Non-Canonical Autophagy (PINCA)
title When the Phagosome Gets Leaky: Pore-Forming Toxin-Induced Non-Canonical Autophagy (PINCA)
title_full When the Phagosome Gets Leaky: Pore-Forming Toxin-Induced Non-Canonical Autophagy (PINCA)
title_fullStr When the Phagosome Gets Leaky: Pore-Forming Toxin-Induced Non-Canonical Autophagy (PINCA)
title_full_unstemmed When the Phagosome Gets Leaky: Pore-Forming Toxin-Induced Non-Canonical Autophagy (PINCA)
title_short When the Phagosome Gets Leaky: Pore-Forming Toxin-Induced Non-Canonical Autophagy (PINCA)
title_sort when the phagosome gets leaky: pore-forming toxin-induced non-canonical autophagy (pinca)
topic Cellular and Infection Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8968195/
https://www.ncbi.nlm.nih.gov/pubmed/35372127
http://dx.doi.org/10.3389/fcimb.2022.834321
work_keys_str_mv AT herbmarc whenthephagosomegetsleakyporeformingtoxininducednoncanonicalautophagypinca
AT gluschkoalexander whenthephagosomegetsleakyporeformingtoxininducednoncanonicalautophagypinca
AT faridalina whenthephagosomegetsleakyporeformingtoxininducednoncanonicalautophagypinca
AT kronkemartin whenthephagosomegetsleakyporeformingtoxininducednoncanonicalautophagypinca