Enteric Nervous System Derived IL-18 Orchestrates Mucosal Barrier Immunity

Mucosal barrier immunity is essential for the maintenance of the commensal microflora and combating invasive bacterial infection. Although immune and epithelial cells are thought to be the canonical orchestrators of this complex equilibrium enteric nervous system (ENS) plays an essential and non-redundant role in governing the anti-microbial protein (AMP) response. Neuron derived IL-18 signaling controls tissue wide intestinal immunity and has profound consequences on the mucosal barrier and invasive bacterial killing. We isolated and characterized mucosal associated and luminal bacterial communities from wild type and neuronal IL18 deficient mice(Il18f/f Hand2+) by. 16S rRNA sequencing of mucosal-associated and luminal bacteria from the same animal showed that in the absence of neuronal IL-18 the composition of mucosal-associated bacteria changed to one more similar to the luminal microbiota than in WT animals. Together these data reveal that neuronal IL-18 driven AMP production is necessary to exclude microbes from the epithelium and maintain a quasi-sterile homeostatic inner mucus layer.