159. Modulation of mucosal immunity by the enteric nervous system

Abstract

Nowhere is the balance between protective inflammation against pathogens and tolerance towards innocuous substances more challenging than at the intestinal. Apart from containing the largest lymphoid organ in the body, the intestine is seen as “a second brain”, with as many neurons as the spinal cord. Our preliminary characterization shows antigen-presenting cells (APCs) in close proximity to neuronal processes in the intestine. These processes extend towards myenteric plexi, where they are contact a previously unappreciated population of APCs. These cells quickly responds to inflammatory stimuli from mucosal pathogens, before bacteria is detected deeper in the intestine. This data suggests that intestinal neurons convey inflammatory signals received at the mucosal surface, preparing the intestinal tissue for a response. We then characterized the behavior and movement of intestinal APCs using intravital multiphoton using fluorescent reporters for enteric neurons and cells of the immune system, in the serosa in steady state, and following non-invasive bacterial challenge in the mucosa. While APCs in the mucosa move in steady state this is not true for serosal APCs. Nonetheless, following challenge in the mucosa, serosal APCs extend dendrites within minutes. This signaling is prevented by pretreatment with tetrodotoxin. Longitudinal signaling is seen between mucosal APCs to serosal cells in a distant (>5 cm) segment. We believe this represents a short loop for controlling and synchronizing responses along the intestine during pathogenic challenge.