Open AccessMaintenance and loss of endocytic organelle integrity: mechanisms and implications for antigen cross-presentation
Author(s) -
Eleanor Childs,
Conor M. Henry,
Johnathan Canton,
Caetano Reis e Sousa
Publication year - 2021
Publication title -
open biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.078
H-Index - 53
ISSN - 2046-2441
DOI - 10.1098/rsob.210194
Subject(s) - endocytic cycle , biology , endosome , microbiology and biotechnology , antigen presentation , cross presentation , phagosome , endocytosis , intracellular , cell , immunology , immune system , t cell , genetics
The membranes of endosomes, phagosomes and macropinosomes can become damaged by the physical properties of internalized cargo, by active pathogenic invasion or by cellular processes, including endocytic maturation. Loss of membrane integrity is often deleterious and is, therefore, prevented by mitigation and repair mechanisms. However, it can occasionally be beneficial and actively induced by cells. Here, we summarize the mechanisms by which cells, in particular phagocytes, try to prevent membrane damage and how, when this fails, they repair or destroy damaged endocytic organelles. We also detail how one type of phagocyte, the dendritic cell, can deliberately trigger localized damage to endocytic organelles to allow for major histocompatibility complex class I presentation of exogenous antigens and initiation of CD8+ T-cell responses to viruses and tumours. Our review highlights mechanisms for the regulation of endocytic organelle membrane integrity at the intersection of cell biology and immunology that could be co-opted for improving vaccination and intracellular drug delivery.