Recent reviews have highlighted the signaling pathways and brain cell types that participate in neuroimmune signaling (Dantzer, 2018; Nisticò et al., 2017; Skaper et al., 2018). Briefly, the innate immune system in the central nervous system (CNS) consists of brain cells adept at recognizing and responding to potential threats in the neuronal microenvironment. Microglia and astrocytes (discussed in detail in later sections) are considered the principal immune mediators in brain, responding to and releasing immune signals, while neurons also express genes and signaling systems that modulate CNS immune responses (Mayfield et al., 2013). A vast array of innate immune signals, such as chemokines and cytokines, danger-associated molecular patterns (DAMPs), and pathogen-associated molecular patterns (PAMPs) activate different families of immune receptors in the brain. Chemokine receptors, cytokine receptors, and pattern recognition receptors (PRR) induce transcription factor signaling and the production of pro- or anti-inflammatory cytokines, chemokines, and other neuromodulators. For example, toll-like receptors (TLRs) are key components of neuroimmune activation. In addition to responding to molecular constituents of microbes, such as the bacterial endotoxin lipopolysaccharide (LPS), TLR4 is stimulated by other
