Menendez Alfredo, Arena Ellen T, Guttman Julian A, Thorson Lisa, Vallance Bruce A, Vogl Wayne, Finlay B Brett
Michael Smith Laboratories, Division of Anatomy and Cell Biology, Life Sciences Centre, University of British Columbia, Vancouver, Canada.
J Infect Dis. 2009 Dec 1;200(11):1703-13. doi: 10.1086/646608.
The gallbladder is often colonized by Salmonella during typhoid fever, yet little is known about bacterial pathogenesis in this organ. With use of a mouse model of acute typhoid fever, we demonstrate that Salmonella infect gallbladder epithelial cells in vivo. Bacteria in the gallbladder showed a unique behavior as they replicated within gallbladder epithelial cells and remained confined to those cells without translocating to the mucosa. Infected gallbladders showed histopathological damage characterized by destruction of the epithelium and massive infiltration of neutrophils, accompanied by a local increase of proinflammatory cytokines. Damage was determined by the ability of Salmonella to invade gallbladder epithelial cells and was independent of high numbers of replication-competent, although invasion-deficient, bacteria in the lumen. Our results establish gallbladder epithelial cells as a novel niche for in vivo replication of Salmonella and reveal the involvement of these cells in the pathogenesis of Salmonella in the gallbladder during the course of acute typhoid fever.
在伤寒热期间，胆囊常被沙门氏菌定植，但对该器官中细菌的发病机制知之甚少。通过使用急性伤寒热小鼠模型，我们证明沙门氏菌在体内感染胆囊上皮细胞。胆囊中的细菌表现出独特的行为，它们在胆囊上皮细胞内复制，并局限于这些细胞内，而不会转移至黏膜。受感染的胆囊表现出组织病理学损伤，其特征为上皮破坏和中性粒细胞大量浸润，同时伴有促炎细胞因子局部增加。损伤取决于沙门氏菌侵入胆囊上皮细胞的能力，并且与管腔内大量具有复制能力但缺乏侵袭能力的细菌无关。我们的结果确立了胆囊上皮细胞是沙门氏菌在体内复制的新位点，并揭示了这些细胞在急性伤寒热病程中参与胆囊内沙门氏菌的发病机制。
