Loss of CNFy toxin-induced inflammation drives Yersinia pseudotuberculosis into persistency

Gastrointestinal infections caused by enteric yersiniae can become persistent and complicated by relapsing enteritis and severe autoimmune disorders. To establish a persistent infection, the bacteria have to cope with hostile surroundings when they transmigrate through the intestinal epithelium and colonize underlying gut-associated lymphatic tissues. How the bacteria gain a foothold in the face of host immune responses is poorly understood. Here, we show that the CNFY toxin, which enhances translocation of the antiphagocytic Yop effectors, induces IL-6-triggered inflammatory responses. This results in extensive tissue destruction, alteration of the intestinal microbiota and bacterial clearance. An elimination of CNFY, however, increases inter-feron-?-mediated responses, comprising non-inflammatory antimicrobial activities and Ido1-promoted tolerogenesis. This process is accompanied by a preterm reprogram-ming of the pathogen's transcriptional response towards persistence, which gives the bacteria a fitness edge against host responses. These results have significant implica-tions for our understanding how enteric bacteria establish a commensal-type life style. Overall design: RNA of Y. pseudotuberculosis infected and uninfected caecal tissue of Mus musculus