Abstract
Many bacterial pathogens hijack macrophages to egress from the port of entry to the lymphatic drainage and/or bloodstream, causing dissemination of life-threatening infections. However, the underlying mechanisms are not well understood. Here, we report that Salmonella infection generates directional electric fields (EFs) in the follicle-associated epithelium of mouse cecum. In vitro application of an EF, mimicking the infection-generated electric field (IGEF), induces directional migration of primary mouse macrophages to the anode, which is reversed to the cathode upon Salmonella infection. This infection-dependent directional switch is independent of the Salmonella pathogenicity island 1 (SPI-1) type III secretion system. The switch is accompanied by a reduction of sialic acids on glycosylated surface components during phagocytosis of bacteria, which is absent in macrophages challenged by microspheres. Moreover, enzymatic cleavage of terminally exposed sialic acids reduces macrophage surface negativity and severely impairs directional migration of macrophages in response to an EF. Based on these findings, we propose that macrophages are attracted to the site of infection by a combination of chemotaxis and galvanotaxis; after phagocytosis of bacteria, surface electrical properties of the macrophage change, and galvanotaxis directs the cells away from the site of infection.
Highlights
We propose that macrophages are attracted to the site of infection by a combination of chemotaxis and galvanotaxis; after phagocytosis of bacteria, the electrical properties of the macrophage change, and galvanotaxis directs the cells away from the site of infection allowing the escape of the macrophages that contain pathogens
Common bacterial pathogens such as Salmonella, Shigella, and Yersinia spp. invade the gut epithelial barrier, preferentially by targeting the relatively small number of M cells located in the follicle-associated epithelium (FAE) [1,2,3]
We report that Salmonella infection generates a directional electric field (EF) at the bacterial entry sites that can recruit macrophages by galvanotaxis
Summary
Common bacterial pathogens such as Salmonella, Shigella, and Yersinia spp. invade the gut epithelial barrier, preferentially by targeting the relatively small number of M cells located in the follicle-associated epithelium (FAE) [1,2,3]. Subsequent phagocytosis and clearance of these pathogens by immune cells usually stops the infection. Some of these bacterial pathogens have developed strategies, such as the type III secretion systems in Salmonella spp. [8,9,10,11,12], to evade macrophage killing and survive inside the macrophage [13,14,15,16], an environment in which the pathogen is hidden from the immune system. Chemotaxis can explain how macrophages reach an infected site, it cannot explain how macrophages harboring pathogens escape from the bacterial entry site to reach the lymphatic drainage and/or bloodstream, a critical initial step in the dissemination process that is understudied and poorly understood
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