Pretreatment of mice with streptomycin provides a Salmonella enterica serovar typhimurium colitis model that allows analysis of both pathogen and host
Pretreatment of mice with streptomycin provides a Salmonella enterica serovar typhimurium colitis model that allows analysis of both pathogen and host
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DOI：
10.1128/iai.71.5.2839-2858.2003
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发表时间：
2003-05-01
影响因子：
3.1
通讯作者：
Hardt, WD
中科院分区：
文献类型：
--
作者：
Barthel, M;Hapfelmeier, S;Hardt, WD
肠道沙门氏菌亚种1血清型鼠伤寒沙门氏菌是人类小肠结肠炎的主要病因。由于未知原因，在小鼠中，血清型鼠伤寒沙门氏菌不会引发肠道炎症，而是靶向肠道相关淋巴组织并引起全身性伤寒样感染。缺乏合适的小鼠模型限制了对肠道沙门氏菌病发病机制的分析。我们在此描述了链霉素预处理的小鼠如何为血清型鼠伤寒沙门氏菌结肠炎提供一个小鼠模型。链霉素预处理小鼠中的血清型鼠伤寒沙门氏菌结肠炎在许多方面类似于人类感染，包括上皮溃疡、水肿、细胞间黏附分子1的诱导以及多形核中性粒细胞/CD18(+)细胞的大量浸润。这种病理变化强烈依赖于通过血清型鼠伤寒沙门氏菌SPI - 1型III分泌系统的蛋白质转运。使用一种缺乏所有淋巴结和有组织的肠道相关淋巴组织的淋巴毒素β受体敲除小鼠品系，我们证明派尔集合淋巴结和肠系膜淋巴结对于小鼠血清型鼠伤寒沙门氏菌结肠炎的起始不是必需的。我们的结果表明，链霉素预处理的小鼠提供了一种独特的感染模型，首次允许使用病原体和宿主的突变体来研究肠道沙门氏菌病的分子机制。
Salmonella enterica subspecies 1 serovar Typhimurium is a principal cause of human enterocolitis. For unknown reasons, in mice serovar Typhimurium does not provoke intestinal inflammation but rather targets the gut-associated lymphatic tissues and causes a systemic typhoid-like infection. The lack of a suitable murine model has limited the analysis of the pathogenetic mechanisms of intestinal salmonellosis. We describe here how streptomycin-pretreated mice provide a mouse model for serovar Typhimurium colitis. Serovar Typhimurium colitis in streptomycin-pretreated mice resembles many aspects of the human infection, including epithelial ulceration, edema, induction of intercellular adhesion molecule 1, and massive infiltration of PMN/CD18(+) cells. This pathology is strongly dependent on protein translocation via the serovar Typhimurium SPH type III secretion system. Using a lymphotoxin beta-receptor knockout mouse strain that lacks all lymph nodes and organized gut-associated lymphatic tissues, we demonstrate that Peyer's patches and mesenteric lymph nodes are dispensable for the initiation of murine serovar Typhimurium colitis. Our results demonstrate that streptomycin-pretreated mice offer a unique infection model that allows for the first time to use mutants of both the pathogen and the host to study the molecular mechanisms of enteric salmonellosis.