Bacterial Modulation of Intestinal Motility through Macrophage Redistribution

Abstract

AbstractIntestinal microbes, whether resident or transient, influence the physiology of their hosts, altering both the chemical and the physical characteristics of the gut. An example of the latter is the human pathogenVibrio cholerae’sability to induce strong mechanical contractions, discovered in zebrafish. The underlying mechanism has remained unknown, but the phenomenon requires the actin crosslinking domain (ACD) ofVibrio’sType VI Secretion System (T6SS), a multicomponent protein syringe that pierces adjacent cells and delivers toxins. By using a zebrafish-nativeVibrioand imaging-based assays of host intestinal mechanics and immune responses, we find that macrophages mediate the connection between the T6SS ACD and intestinal activity: ACD-dependent tissue damage activates macrophages and recruits them from their unperturbed positions near enteric neurons lining the midgut, spurring strong gut contractions resembling those resulting from genetic depletion of macrophages. In addition to illuminating host-directed actions of the widespread T6SS protein apparatus, our findings highlight how localized bacteria-induced injury can reshape neuro-immune cellular dynamics to impact whole-organ physiology.