Meeting Abstract

S8.3-1  Monday, Jan. 6 13:30  Early-Life Programming of Neuroendocrine Function by the Immune System: Plasticity or Autoimmunity due to Biome Depletion? BILBO, S.D.*; WILLIAMSON, L.L.; PARKER, W.; Duke University; Duke University; Duke University staci.bilbo@duke.edu

Immune molecules have a powerful impact on neuroendocrine function during health as well as sickness. Microglia are the primary immunocompetent cells of the brain, and rapidly respond to any infection, injury or perturbation of homeostasis via a dynamic process of activation. These functional shifts are thought to be evolved, adaptive responses that organize changes in behavior and mobilize immune resources, but can also lead to pathology or exacerbate disease if prolonged or exaggerated. The developing brain in particular is exquisitely sensitive to both endogenous and exogenous signals, and increasing evidence suggests the immune system has a critical role in brain development and associated behavioral outcomes for the life of the individual. We have demonstrated that a single bacterial infection early in life can program neuroendocrine function and impair cognition throughout the remainder of the lifespan in rodents, and that these changes are causally linked to enduring changes in microglial function. However, it is unclear whether these changes represent developmental plasticity, as many aspects of the sensitized phenotype of the microglia suggest autoimmunity. A wide range of diseases associated with a hyperactive immune system are now pandemic in post-industrial society. Increasing evidence points to a profound depletion in the human biome, particularly those organisms living in a symbiotic relationship with all humans prior to the industrial revolution, as the underlying cause that leaves many individuals susceptible to these pandemics of immune-related disease. This talk will consider the evidence that “developmental programming” of microglial function by early-life infection may be a pathological consequence of biome depletion, rather than plasticity in the face of early-life immune exposures.