New Insights into Microglia–Neuron Interactions: A Neuron’s Perspective

Abstract

Microglia are the primary immune cells of the central nervous system. However, recent data indicate that microglia also contribute to diverse physiological and pathophysiological processes that extend beyond immune-related functions and there is a growing interest to understand the mechanisms through which microglia interact with other cells in the brain. In particular, the molecular processes that contribute to microglia-neuron communication in the healthy brain and their role in common brain diseases have been intensively studied during the last decade. In line with this, fate-mapping studies, genetic models and novel pharmacological approaches have revealed the origin of microglial progenitors, demonstrated the role of self-maintaining microglial populations during brain development or in adulthood, and identified the unexpectedly long lifespan of microglia that may profoundly change our view about senescence and age-related human diseases. Despite the exponentially increasing knowledge about microglia, the role of these cells in health and disease is still extremely controversial and the precise molecular targets for intervention are not well defined. This is in part due to the lack of microglia-specific manipulation approaches until very recently and to the high level of complexity of the interactions between microglia and other cells in the brain that occur at different temporal and spatial scales. In this review, we briefly summarize the known physiological roles of microglia-neuron interactions in brain homeostasis and attempt to outline some major directions and challenges of future microglia research.

Environmental Signals on Microglial Function during Brain Development, Neuroplasticity, and Disease

“…Besides that, microglia shift from different stages of activation also depends on a cross-talk between neurons, astrocytes, and microglial cells, which is essential for adaptive neuroplasticity. Neurons are able to inform microglia about their status, controlling their activation and motility through the secretion of soluble factors, extracellular vesicles, or contact-dependent mechanisms [21]. In the healthy brain, the surveillant microglia are under the control of neuronal factors, such as CD200 and fractalkine (CX3CL1) [22].…”

Neuroimmune Activation Drives Multiple Brain States

“…Astrocytes provide energy and regulate glutamate during synaptic transmission and plasticity (Suzuki et al, 2011; Gold, 2014; Nortley and Attwell, 2017; Alberini et al, 2018). Microglia provide continuous surveillance, synaptic pruning, and regulation of synaptic plasticity via complement and cytokine interactions (Nimmerjahn et al, 2005; Wu et al, 2015; Lenz and Nelson, 2018; Pósfai et al, 2018). Importantly, neurons produce and have receptors for “immune” proteins including cytokines, chemokines and complement, thereby providing a basis for ongoing communication with glial cells (Freidin et al, 1992; Veerhuis et al, 2011; McCusker and Kelley, 2013; Paolicelli et al, 2014).…”

Microglia-precursor cell interactions in health and in pathology

“…The early microglia colonization of the CNS has led researchers to speculate about their roles in the fundamental developmental processes of neurogenesis, gliogenesis, vasculogenesis and angiogenesis. Microglia constantly interrogate and respond to cells in their environments, which could serve to communicate developmental tasks to microglia (Reemst et al, 2016;Posfai et al, 2018). Therefore, we can formulate the following questions: Do microglia have any preference for a particular cell type or cell stage or cell status?…”