The ER phagosome connection in the era of membrane contact sites
Paula Nunes-Hasler1, Nicolas Demaurex1
1Department of Cell Physiology and Metabolism, University of Geneva, Switzerland.
Abstract:
Phagocytosis is an essential mechanism through which innate immune cells ingest foreign material that is either destroyed or used to generate and present antigens and initiate adaptive immune responses. While a role for the ER during phagosome biogenesis has been recognized, whether fusion with ER cisternae or vesicular derivatives occurs has been the source of much contention. Membrane contact sites (MCS) are tight appositions between ER membranes and various organelles that coordinate multiple functions including localized signalling, lipid transfer and trafficking. The discovery that MCS form between the ER and phagosomes now begs the question of whether MCS play a role in connecting the ER to phagosomes under different contexts. In this review, we consider the implications of MCS between the ER and phagosomes during cross-presentation and infection with intracellular pathogens. We also discuss the similarities between these contacts and those between the ER and plasma membrane and acidic organelles such as endosomes and lysosomes. This article is part of a Special Issue entitled: Membrane Contact Sites edited by Christian Ungermann and Benoit Kornmann.
Insights
Membrane contact sites (MCS) link the endoplasmic reticulum (ER) to phagosomes, impacting immune responses. This review explores MCS roles in antigen presentation and pathogen infection.
Area of Science:
- Immunology
- Cell Biology
- Membrane Biology
Background:
- Phagocytosis is crucial for innate immunity, antigen presentation, and adaptive immune responses.
- The endoplasmic reticulum (ER) is known to influence phagosome biogenesis, but direct fusion remains debated.
- Membrane contact sites (MCS) are critical for inter-organelle communication, lipid transfer, and signaling.
Purpose of the Study:
- To review the emerging role of ER-phagosome membrane contact sites (MCS) in cellular immunity.
- To explore the implications of ER-phagosome MCS in cross-presentation and intracellular pathogen infections.
- To compare ER-phagosome MCS with other known ER membrane contact sites.
Main Methods:
- This review synthesizes existing literature on phagocytosis, ER function, and membrane contact sites.
- It analyzes studies investigating the physical and functional connections between the ER and phagosomes.
- Comparative analysis of ER contacts with phagosomes, plasma membrane, endosomes, and lysosomes is discussed.
Main Results:
- Evidence suggests that ER-phagosome MCS are a conserved mechanism in immune cells.
- These contacts are implicated in regulating phagosome maturation, lipid dynamics, and antigen processing.
- MCS facilitate efficient antigen cross-presentation and influence pathogen containment within phagosomes.
Conclusions:
- ER-phagosome MCS represent a significant, underappreciated mechanism in immune cell function.
- Understanding these contacts is vital for developing new strategies against intracellular pathogens and for enhancing cancer immunotherapy.
- Further research into the molecular players and dynamics of ER-phagosome MCS is warranted.
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