Decoding Mast Cell-Microglia Communication in Neurodegenerative Diseases

Abstract

Microglia, resident immune cells of the central nervous system (CNS), play a pivotal role in immune surveillance and maintenance of neuronal health. Mast cells are also important resident immune cells of the CNS but they are underappreciated and understudied. Both microglia and mast cells are endowed with an array of signaling receptors that recognize microbes and cellular damage. As cellular sensors and effectors in the CNS, they respond to many CNS perturbations and have been implicated in neuroinflammation and neurodegeneration. Mast cells contain numerous secretory granules packaged with a plethora of readily available and newly synthesized compounds known as ‘mast cell mediators’. Mast cells act as ‘first responders’ to a pathogenic stimuli and respond by degranulation and releasing these mediators into the extracellular milieu. They alert other glial cells, including microglia to initiate neuroinflammatory processes that culminate in the resolution of injury. However, failure to resolve the pathogenic process can lead to persistent activation, release of pro-inflammatory mediators and amplification of neuroinflammatory responses, in turn, resulting in neuronal dysfunction and demise. This review discusses the current understanding of the molecular conversation between mast cells and microglia in orchestrating immune responses during two of the most prevalent neurodegenerative diseases, namely Alzheimer’s disease and Parkinson’s disease. Here we also survey the potential emerging therapeutic approaches targeting common pathways in mast cells and microglia to extinguish the fire of inflammation.