New insights into the role of the endoplasmic reticulum in microglia

Abstract

Microglial cells are the only resident immune cells in the central nervous system and constitute its frontline guardian. They are extremely reactive against infections, trauma, or toxins, but are also responsible for mediating inflammation, taking part in the pathogenic course of many neuropathologies (Sierra et al., 2019). Cell-specific staining, ultrastructural analysis by transmission electron microscopy (TEM), or two-photon-microscopy imaging have been relevant for the characterization of microglia as well as their cell-cell interactions, which have led to a better understanding of microglial roles in health and disease. Nowadays, we know that microglia are very dynamic cells that require a well-developed endomembrane system to respond to a plethora of stimuli and perform their major biological functions, e.g., self-renewal, migration to the damaged area, phagocytic activity, production, and release of anti- or pro-inflammatory cytokines, etc. According to the type and severity of the stimulation trigger, microglia can drastically change in morphology in the adult brain: They transform from branched tiny cells with homeostatic functions to cells with an amoeboid appearance due to retraction of their processes and enlargement of the cell body, which are more correlated with a pro-inflammatory phenotype. Among all the endomembranous compartments in microglia, the endoplasmic reticulum (ER) can be considered as a key organelle governing cellular metabolism, but recent evidence also points to a crucial role in modulating specific microglial functions.