Enteropathogenic Escherichia coli (EPEC) belong to the attaching and effacing (A/E) family of bacterial pathogens that represent a worldwide health concern. These non-invasive bacteria attach to intestinal enterocytes through a type III secretion system (T3SS), leading to intestinal inflammation and severe diarrhea. To dissect the signals leading to the induction of the inflammatory response and to understand its role in the pathogenesis of infection, we used the rabbit model, which represents a close model of human infections. Rabbits were orally inoculated with either the wild type O103:K-:H2 E22 EPEC strain or with the E22Δtir/espB strain, which bears mutations in two genes involved in the injectisome structure and function. To monitor the development of the inflammatory response, we developed a quantitative real-time RT-PCR (qPCR) assay specific for a panel of rabbit genes. Using combined immunohistochemistry and qPCR, we show here that the inflammatory response triggered by wild type EPEC occurs very early, preceding the bacterial colonization of the epithelium. However, this early response is unable to prevent bacterial attachment on enterocytes. Moreover, our results show that expression of a complete bacterial injectisome is required for the development of inflammation. Finally, infection by the virulent strain, but not by the doubly mutated strain, rapidly induces the development of a specific immune response in the mesenteric lymph nodes, which is not associated with protection. Our findings suggest that the induction of a strong inflammatory response by T3SS dependent components represents a selective advantage for T3SS+ bacteria, thereby facilitating their colonization.
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