Commensal E. coli induced colonization resistance against mucosal Salmonella infection

Salmonella is the causative agent in Salmonellosis and is a leading cause of gastrointestinal bacterial infections worldwide. During mucosal Salmonella infection Salmonella must first establish a niche in the gastrointestinal tract in order to initiate infection. Colonization resistance (CR), defined as the ability of intestinal microbiota and host defenses to protect against pathogens, is the first line defense against intestinal infection. The mechanism for commensal bacteria mediated CR has been studied for a long time; however, only a few studies have explored how microbiota can induce CR against Salmonella infection. Herein we demonstrate that a mouse commensal E. coli strain mediates CR against mucosal Salmonella Typhimurium infection, and that this CR is independent of the inflammasome, TLR5, MyD88, adaptive immunity, and a complex microbiome. The commensal E. coli strain does not directly compete with Salmonella growth in vitro , and is only capable of inducing colonization resistance in vivo . Gene expression analysis demonstrates that colonization of mice by commensal E. coli induces a large number of host defense genes involved in the regulation of mucosal barriers, innate immune cells and arachidonic acid metabolism. Our studies demonstrate that commensal E. coli interacts with the host through a novel pathway to induce CR against mucosal Salmonella infection and illuminate the complex interactions between microbiota and the host that shape defenses and defend against enteric infections.