Tac1 Deficiency Reduces the Severity of Enteric Bacterial Infection

Abstract

BackgroundInfection with enteric bacterial pathogens continues to cause significant morbidity and mortality throughout the world. These pathogens include enterohemorrhagic and enteropathogenic Escherichia coli, which transit the intestinal tract, efface microvilli, and attach firmly to intestinal epithelial cells predominantly in the colon. Investigation of these human-adapted pathogens has been greatly aided by mouse models of infection. The mouse-adapted attaching and effacing pathogen Citrobacter rodentium utilizes many similar mechanisms of pathogenesis, including the use of a type III secretion system, and virulence factors encoded in a locus of enterocyte effacement. Although this model has allowed for assessing the complexity of the host response, the complex interplay between the nervous and immune systems in response to infection remains incomplete. MethodsWe assessed the role of sensory neurotransmitters encoded by the Tac1 gene in the host response to C. rodentium. ResultsTac1-deficient mice had significantly reduced pathogen shedding and colonic bacterial burden, accompanied by decreased expression of inflammatory cytokines and chemokines. In accordance with reduced chemokine production, we observed reduced colonic recruitment of specific immune cell populations in Tac1-/- compared to WT mice. ConclusionsSensory neuropeptides regulate key aspects of enteric bacterial infection and may serve as unique targets in the treatment of enteric disease.