Gallbladder Epithelium as a Niche for Chronic Salmonella Carriage
Gallbladder Epithelium as a Niche for Chronic Salmonella Carriage
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DOI：
10.1128/iai.00258-13
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发表时间：
2013-08-01
影响因子：
3.1
通讯作者：
Gunn, John S.
中科院分区：
文献类型：
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作者：
Gonzalez-Escobedo, Geoffrey;Gunn, John S.
尽管对伤寒进行了深入研究，但慢性伤寒携带仍然是该疾病在流行地区传播和持续存在的一个问题。这种慢性状态与受感染携带者胆囊中的胆结石高度相关，沙门氏菌可在其上形成坚固的生物膜。然而，我们假设除了胆结石外，胆囊上皮也有助于慢性运输的建立/维持。在这项工作中，我们提出了胆囊上皮在慢性运输中的作用的证据，其机制包括侵袭、细胞内持久性和生物膜的形成。无论胆汁是否存在，沙门氏菌都能以依赖于沙门氏菌致病性岛1 （SPI-1）的方式附着并侵袭极化的胆囊上皮细胞。沙门氏菌在侵袭后12和24 h的细胞内复制也很明显。一个流动系统显示，早在接种后12小时，沙门氏菌就能粘附在胆囊上皮细胞上并形成广泛的细菌灶。慢性伤寒携带小鼠模型的体内实验显示，在沙门氏菌感染后2个月，胆囊上皮和固有层受到侵袭和损伤，巨噬细胞大量存在，中性粒细胞相对缺乏，感染上皮细胞挤压。此外，感染后21天，小鼠胆囊上皮表面可见沙门氏菌细胞的微菌落。这些数据揭示了沙门氏菌在胆囊内维持的第二个潜在机制，即细胞内持久性和/或细菌聚集在胆囊上皮内/上，并伴有腔内细胞挤压。
Although typhoid fever has been intensively studied, chronic typhoid carriage still represents a problem for the transmission and persistence of the disease in areas of endemicity. This chronic state is highly associated with the presence of gallstones in the gallbladder of infected carriers upon which Salmonella can form robust biofilms. However, we hypothesize that in addition to gallstones, the gallbladder epithelium aids in the establishment/maintenance of chronic carriage. In this work, we present evidence of the role of the gallbladder epithelium in chronic carriage by a mechanism involving invasion, intracellular persistence, and biofilm formation. Salmonella was able to adhere to and invade polarized gallbladder epithelial cells apically in the absence and presence of bile in a Salmonella pathogenicity island 1 (SPI-1)-dependent manner. Intracellular replication of Salmonella was also evident at 12 and 24 h postinvasion. A flowthrough system revealed that Salmonella is able to adhere to and form extensive bacterial foci on gallbladder epithelial cells as early as 12 h postinoculation. In vivo experiments using a chronic mouse model of typhoid carriage showed invasion and damage of the gallbladder epithelium and lamina propria up to 2 months after Salmonella infection, with an abundant presence of macrophages, a relative absence of neutrophils, and extrusion of infected epithelial cells. Additionally, microcolonies of Salmonella cells were evident on the surface of the mouse gallbladder epithelia up to 21 days postinfection. These data reveal a second potential mechanism, intracellular persistence and/or bacterial aggregation in/on the gallbladder epithelium with luminal cell extrusion, for Salmonella maintenance in the gallbladder.