Tac1 deficiency reduces the severity of enteric bacterial infection

Infection with enteric bacterial pathogens continues to cause significant morbidity and mortality throughout the world. Effective control of these infections requires coordinated immune responses that are shaped in part by bidirectional communication between the nervous and immune systems. Sensory neurons are now well appreciated to detect inflammatory or microbial stimuli in numerous organ systems, including the gastrointestinal (GI) tract, and for eliciting the recruitment or activation of specific immune cells. Central to the host protective effect of these neuroimmune circuits is the localized release of neurotransmitters that activate substance P (SP) receptor signaling. However, the precise contribution of sensory neuropeptides encoded by the Tac1 gene, such as SP, in the host response to enteric infection remains incompletely understood.

The role of the Tac1-encoded sensory neurotransmitters in the host response to Citrobacter rodentium was assessed using Tac1-/- and wildtype (WT) mice. Infection and inflammation were determined by bacterial enumeration, histopathology, qPCR, and flow cytometry.

Tac1-/- mice had significantly reduced pathogen shedding and colonic bacterial burden, accompanied by decreased expression of inflammatory cytokines and chemokines compared to WT controls. In accordance with reduced chemokine production, we observed reduced colonic recruitment of neutrophils, monocytes, and IFNγ- and IL-17A-producing T-cells in Tac1-/- compared with WT mice. This reduced immune response was associated with markedly reduced colonic histopathology.

Sensory neuropeptides encoded by Tac1 regulate key aspects of the immune response to enteric bacterial infection and may serve as unique targets in the treatment of enteric disease.