BACKGROUND: Shigella species are invasive human pathogens that cause acute rectocolitis by triggering a dysregulated inflammatory reaction in the colonic and rectal mucosa. Because mice are naturally resistant to shigellosis, there is no mouse model that mimics human disease. We explore the susceptibility of intestinal flora-depleted mice to shigellosis after intragastric infection with Shigella strains. METHODS: Mice given 5 g/L streptomycin as a beverage were infected intragastrically with 1 x 108 cfu of either invasive or noninvasive Shigella strains. RESULTS: We found that invasive Shigella strains persist up to 30 days in feces, whereas the persistence of noninvasive Shigella strains was reduced. Colonization primarily involves the colon and the cecum and, to a lesser extent, the ileum. The hallmark of inflammation in the intestinal tissue is a dramatic expansion of the lymphoid follicles, in which a high apoptotic index is recorded. CONCLUSIONS: We provide a murine model in which shigellae are able to reach their natural tissue target: the colon. Moreover, the absence of polymorphonuclear leukocyte recruitment and of epithelial cell lesions reveal some aspects of shigellosis that are usually hidden by the prevalence of this cell population. This novel model may contribute to the identification of new targets for vaccines and therapies.
BACKGROUND: Shigella species are invasive human pathogens that cause acute rectocolitis by triggering a dysregulated inflammatory reaction in the colonic and rectal mucosa. Because mice are naturally resistant to shigellosis, there is no mouse model that mimics human disease. We explore the susceptibility of intestinal flora-depleted mice to shigellosis after intragastric infection with Shigella strains. METHODS:Mice given 5 g/L streptomycin as a beverage were infected intragastrically with 1 x 108 cfu of either invasive or noninvasive Shigella strains. RESULTS: We found that invasive Shigella strains persist up to 30 days in feces, whereas the persistence of noninvasive Shigella strains was reduced. Colonization primarily involves the colon and the cecum and, to a lesser extent, the ileum. The hallmark of inflammation in the intestinal tissue is a dramatic expansion of the lymphoid follicles, in which a high apoptotic index is recorded. CONCLUSIONS: We provide a murine model in which shigellae are able to reach their natural tissue target: the colon. Moreover, the absence of polymorphonuclear leukocyte recruitment and of epithelial cell lesions reveal some aspects of shigellosis that are usually hidden by the prevalence of this cell population. This novel model may contribute to the identification of new targets for vaccines and therapies.
Authors: Jonathan N Pruneda; F Donelson Smith; Angela Daurie; Danielle L Swaney; Judit Villén; John D Scott; Andrew W Stadnyk; Isolde Le Trong; Ronald E Stenkamp; Rachel E Klevit; John R Rohde; Peter S Brzovic Journal: EMBO J Date: 2014-01-20 Impact factor: 11.598
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Authors: L Lembo-Fazio; G Nigro; G Noël; G Rossi; F Chiara; K Tsilingiri; M Rescigno; A Rasola; M L Bernardini Journal: Cell Death Dis Date: 2011-02-24 Impact factor: 8.469
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