Neuroimmune signaling contributes to enteric, sensory, endocrine hypothalamic-adrenal (HPA) responses to external and internal environmental factors. Monocytes and brain microglia, are sensitive key cells involved in innate immune signaling. Neuroimmune signaling through microglia and other monocyte-like cells integrates sensory and endocrine enteric responses with brain. Microglia are unique monocyte-macrophage-like cells that share multiple stages of activation reflected morphologically and in gene expression (Hingson et al. 2009; Graeber 2010). Microglia are formed embryonically and migrate to fetal brain early in development creating a unique self-renewing monocyte-like cell that is maintained by self-renewal. Microglia and vascular monocyte-macrophages are the primary innate immune cells in brain (Ransohoff and Cardona 2010). Healthy brain contains ramified “resting” microglia known to survey brain and regulate synapses (Graeber 2010). Microglia have a low threshold of activation with initial states secreting signaling molecules, increasing expression of Major Histocompatibility Complex (MHC) proteins and Toll-like receptor proteins (TLR), key proteins involved in innate immune amplification. Morphological activation states show cellular enlargement, increased cell matrix and adhesion protein expression and progressive induction of other specific genes. Efforts to establish subtypes of
