Bacterial Modulation of Intestinal Motility through Macrophage Redistribution

Gut microbes interact with each other and with host cells, including cells of the immune system. Experiments in larval zebrafish revealed that the pathogen Vibrio cholerae can induce remarkably strong intestinal contractions, an effect that requires the actin cross-linking domain (ACD) of the bacteria’s Type VI Secretion System, a syringe-like apparatus inserted into target cells. The connection between bacterial components and host mechanical response, however, has remained unclear. Through live imaging, we show that macrophages provide this link. Depletion of macrophages leads to strong gut contractions, consistent with prior work showing that macrophages regulate enteric neurons’ coordination of gut dynamics. A zebrafish-native Vibrio species causes tissue damage at the gut posterior, induces strong contractions, and leads to a redistribution of macrophages from the midgut to the posterior; all these effects require the ACD. These observations imply that microbes can modulate host mechanics by shifting the macrophage distribution, leading to local sparsity around midgut neurons and therefore an enhancement of intestinal contractions, a mechanism based on physical reorganization rather than modulation of biochemical signaling for its effects.