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首页> 外文期刊>Infection and immunity >Intimin-Specific Immune Responses Prevent Bacterial Colonization by the Attaching-Effacing PathogenCitrobacter rodentium
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Intimin-Specific Immune Responses Prevent Bacterial Colonization by the Attaching-Effacing PathogenCitrobacter rodentium

机译：内膜特异性免疫反应可防止因附着的病原菌引起的细菌定殖

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The formation of attaching and effacing (A/E) lesions on gut enterocytes is central to the pathogenesis of enterohemorrhagic (EHEC)Escherichia coli, enteropathogenic E. coli (EPEC), and the rodent pathogen Citrobacter rodentium. Genes encoding A/E lesion formation map to a chromosomal pathogenicity island termed the locus of enterocyte effacement (LEE). Here we show that the LEE-encoded proteins EspA, EspB, Tir, and intimin are the targets of long-lived humoral immune responses in C. rodentium-infected mice. Mice infected with C. rodentium developed robust acquired immunity and were resistant to reinfection with wild-type C. rodentium or a C. rodentium derivative, DBS255(pCVD438), which expressed intimin derived from EPEC strain E2348/69. The receptor-binding domain of intimin polypeptides is located within the carboxy-terminal 280 amino acids (Int280). Mucosal and systemic vaccination regimens using enterotoxin-based adjuvants were employed to elicit immune responses to recombinant Int280α from EPEC strain E2348/69. Mice vaccinated subcutaneously with Int280α, in the absence of adjuvant, were significantly more resistant to oral challenge with DBS255(pCVD438) but not with wild-type C. rodentium. This type-specific immunity could not be overcome by employing an exposed, highly conserved domain of intimin (Int388–667) as a vaccine. These results show that anti-intimin immune responses can modulate the outcome of a C. rodentium infection and support the use of intimin as a component of a type-specific EPEC or EHEC vaccine.
机译：肠道肠上皮细胞附着和脱落（A / E）损伤的形成是肠出血性（EHEC）大肠杆菌肠致病性 E发病机理的关键。大肠埃希氏杆菌（EPEC）和啮齿动物病原体（Cemtrobacter rodentium）。编码A / E病变形成的基因映射到一个染色体致病岛，称为肠上皮细胞受损（LEE）。在这里，我们显示LEE编码的蛋白EspA，EsB，Tir和intimin是 C中长寿命体液免疫反应的目标。感染了啮齿动物的小鼠。感染 C的小鼠。啮齿动物具有很强的后天免疫力，并且对野生型 C的再感染具有抵抗力。啮齿动物或 C。 ent衍生物，DBS255（pCVD438），表达源自EPEC株E2348 / 69的内膜素。内膜蛋白多肽的受体结合结构域位于羧基末端的280个氨基酸（Int280）内。使用基于肠毒素的佐剂的粘膜和全身疫苗接种方案来引发对来自EPEC株E2348 / 69的重组Int280α的免疫应答。在没有佐剂的情况下，用Int280α皮下接种的小鼠对DBS255（pCVD438）的口服攻击具有更强的抵抗力，而对野生型 C则没有抵抗力。啮齿动物。通过使用暴露的高度保守的intimin域（Int​​ 388-667 ）作为疫苗，无法克服这种类型特异性的免疫力。这些结果表明，抗内膜免疫反应可以调节 C的结果。啮齿类动物感染并支持使用intimin作为特定类型的EPEC或EHEC疫苗的组成部分。

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