Cargando…

The Delivery of Extracellular “Danger” Signals to Cytosolic Sensors in Phagocytes

Phagocytes, such as macrophages and dendritic cells, possess the ability to ingest large quantities of exogenous material into membrane-bound endocytic organelles such as macropinosomes and phagosomes. Typically, the ingested material, which consists of diverse macromolecules such as proteins and nu...

Descripción completa

Detalles Bibliográficos
Autores principales: Gonzales, Gerone A., Canton, Johnathan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9329928/
https://www.ncbi.nlm.nih.gov/pubmed/35911757
http://dx.doi.org/10.3389/fimmu.2022.944142
_version_ 1784758035618463744
author Gonzales, Gerone A.
Canton, Johnathan
author_facet Gonzales, Gerone A.
Canton, Johnathan
author_sort Gonzales, Gerone A.
collection PubMed
description Phagocytes, such as macrophages and dendritic cells, possess the ability to ingest large quantities of exogenous material into membrane-bound endocytic organelles such as macropinosomes and phagosomes. Typically, the ingested material, which consists of diverse macromolecules such as proteins and nucleic acids, is delivered to lysosomes where it is digested into smaller molecules like amino acids and nucleosides. These smaller molecules can then be exported out of the lysosomes by transmembrane transporters for incorporation into the cell’s metabolic pathways or for export from the cell. There are, however, exceptional instances when undigested macromolecules escape degradation and are instead delivered across the membrane of endocytic organelles into the cytosol of the phagocyte. For example, double stranded DNA, a damage associated molecular pattern shed by necrotic tumor cells, is endocytosed by phagocytes in the tumor microenvironment and delivered to the cytosol for detection by the cytosolic “danger” sensor cGAS. Other macromolecular “danger” signals including lipopolysaccharide, intact proteins, and peptidoglycans can also be actively transferred from within endocytic organelles to the cytosol. Despite the obvious biological importance of these processes, we know relatively little of how macromolecular “danger” signals are transferred across endocytic organelle membranes for detection by cytosolic sensors. Here we review the emerging evidence for the active cytosolic transfer of diverse macromolecular “danger” signals across endocytic organelle membranes. We will highlight developing trends and discuss the potential molecular mechanisms driving this emerging phenomenon.
format Online
Article
Text
id pubmed-9329928
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-93299282022-07-29 The Delivery of Extracellular “Danger” Signals to Cytosolic Sensors in Phagocytes Gonzales, Gerone A. Canton, Johnathan Front Immunol Immunology Phagocytes, such as macrophages and dendritic cells, possess the ability to ingest large quantities of exogenous material into membrane-bound endocytic organelles such as macropinosomes and phagosomes. Typically, the ingested material, which consists of diverse macromolecules such as proteins and nucleic acids, is delivered to lysosomes where it is digested into smaller molecules like amino acids and nucleosides. These smaller molecules can then be exported out of the lysosomes by transmembrane transporters for incorporation into the cell’s metabolic pathways or for export from the cell. There are, however, exceptional instances when undigested macromolecules escape degradation and are instead delivered across the membrane of endocytic organelles into the cytosol of the phagocyte. For example, double stranded DNA, a damage associated molecular pattern shed by necrotic tumor cells, is endocytosed by phagocytes in the tumor microenvironment and delivered to the cytosol for detection by the cytosolic “danger” sensor cGAS. Other macromolecular “danger” signals including lipopolysaccharide, intact proteins, and peptidoglycans can also be actively transferred from within endocytic organelles to the cytosol. Despite the obvious biological importance of these processes, we know relatively little of how macromolecular “danger” signals are transferred across endocytic organelle membranes for detection by cytosolic sensors. Here we review the emerging evidence for the active cytosolic transfer of diverse macromolecular “danger” signals across endocytic organelle membranes. We will highlight developing trends and discuss the potential molecular mechanisms driving this emerging phenomenon. Frontiers Media S.A. 2022-07-14 /pmc/articles/PMC9329928/ /pubmed/35911757 http://dx.doi.org/10.3389/fimmu.2022.944142 Text en Copyright © 2022 Gonzales and Canton 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 Immunology
Gonzales, Gerone A.
Canton, Johnathan
The Delivery of Extracellular “Danger” Signals to Cytosolic Sensors in Phagocytes
title The Delivery of Extracellular “Danger” Signals to Cytosolic Sensors in Phagocytes
title_full The Delivery of Extracellular “Danger” Signals to Cytosolic Sensors in Phagocytes
title_fullStr The Delivery of Extracellular “Danger” Signals to Cytosolic Sensors in Phagocytes
title_full_unstemmed The Delivery of Extracellular “Danger” Signals to Cytosolic Sensors in Phagocytes
title_short The Delivery of Extracellular “Danger” Signals to Cytosolic Sensors in Phagocytes
title_sort delivery of extracellular “danger” signals to cytosolic sensors in phagocytes
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9329928/
https://www.ncbi.nlm.nih.gov/pubmed/35911757
http://dx.doi.org/10.3389/fimmu.2022.944142
work_keys_str_mv AT gonzalesgeronea thedeliveryofextracellulardangersignalstocytosolicsensorsinphagocytes
AT cantonjohnathan thedeliveryofextracellulardangersignalstocytosolicsensorsinphagocytes
AT gonzalesgeronea deliveryofextracellulardangersignalstocytosolicsensorsinphagocytes
AT cantonjohnathan deliveryofextracellulardangersignalstocytosolicsensorsinphagocytes