Microglia Ontology and Signaling

Abstract

Microglia constitute the powerhouse of the innate immune system in the brain. It is now widely accepted that they are monocytic-derived cells that infiltrate the developing brain at the early embryonic stages, and acquire a resting phenotype characterized by the presence of dense branching processes, called ramifications. Microglia use these dynamic ramifications as sentinels to sense and detect any occurring alteration in brain homeostasis. Once a danger signal is detected, such as molecular factors associated to brain damage or infection, they get activated by acquiring a less ramified phenotype, and mount adequate responses that range from phagocyting cell debris to secreting inflammatory and trophic factors. Here, we review the origin of microglia and we summarize the main molecular signals involved in controlling their function under physiological conditions. In addition, their implication in the pathogenesis of multiple sclerosis and stress is discussed.

Keywords: brain; developmental biology; innate immunity; microglia origin; signaling pathways.

Figure 1

The physiological role of microglia. The neurovascular unit (NVU), which is constituted of tightly sealed endothelial cells, basal lamina, pericytes, astrocyte-endfeet, microglia, and neurons, plays a central role in maintaining brain homeostasis and functioning. In the non-neuropathological conditions, microglia use their dynamic processes to constantly survey and screen the microenvironment within the NVU. Microglia are fully equipped to detect a wide range of signals associated to an altered brain homeostasis. In addition, they actively and dynamically communicate with neurons and play an important role in supporting their functions. Importantly, their physiological role in the intact brain can be altered by several intrinsic factors, such as aging, epigenetics, and genetics. This figure has been adapted from ElAli and Rivest (2015).

Figure 2

Microglial signaling and function. A diagram illustrating the main receptor-mediated signaling associated with respective microglial cellular functions.