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 endogenous danger signals, including high-mobility group box 1 (HMGB1), a cytokine-like signaling molecule (Crews et al., 2013; Yu et al., 2006). TLR4 activation typically leads to nuclear translocation of the transcription factor, nuclear factor kappa light-chain-enhancer of activated B cells (NF-κB). NF-κB regulates the expression of pro-inflammatory cytokines, including tumor necrosis factor alpha (TNF-α), interleukin 1-beta (IL-1β), and interleukin 6 (IL-6) (Lu et al., 2008). TLR4 regulates specific subsets of genes depending on distinct combinations of adaptor proteins. Several other pathways (e.g., TNF-α, IL-1, TLR2) also modulate NF-κB, while IL-6 and TLR3, for example, activate distinct transcription factors to induce gene expression. Enhanced expression of NADPH oxidase, reactive oxygen species (ROS) production, inducible nitric oxide synthase (iNOS), and Nod-like receptor protein 3 (NLRP3) inflammasome signaling are other consequences of immune activation which feed for-ward to perpetuate inflammation (Montesinos et al., 2016a). Importantly, the production of anti-inflammatory factors, such as interleukin-10 (IL-10) and transforming growth factor beta (TGF-β), is critical to
