Immunization of Mice with Lactobacillus casei Expressing a Beta-Intimin Fragment Reduces Intestinal Colonization by Citrobacter rodentium
Immunization of Mice with Lactobacillus casei Expressing a Beta-Intimin Fragment Reduces Intestinal Colonization by Citrobacter rodentium
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DOI：
10.1128/cvi.05262-11
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发表时间：
2011-11-01
影响因子：
--
通讯作者：
Oliveira, M. L. S.
中科院分区：
文献类型：
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作者：
Ferreira, P. C. D.;da Silva, J. B.;Oliveira, M. L. S.
肠致病性大肠杆菌（EPEC）是发展中国家儿童腹泻的常见原因。细菌与肠细胞的紧密粘附通过粘附素紧密蛋白与暴露在细胞表面上的TIR受体的结合而发生。在这里，表达β-内膜蛋白片段的干酪乳杆菌（L. casei-Int（cv））作为粘膜疫苗在小鼠中进行抗鼠病原体啮齿柠檬酸杆菌（Citrobacterrodentium）肠道定殖的试验。用L. casei-Int（cv）在粪便中诱导抗Int（cv）伊加，但在血清中不诱导IgG。相反，用纯化的Int（cv）舌下免疫后，在小鼠血清中诱导抗Int（cv）IgG。所有疫苗均能降低C.从粪便中回收啮齿动物。然而，这种减少在用L. casei-Int（CV）通过舌下途径。这些小鼠在感染后10天还显示脾细胞的白细胞介素6（IL-6）和γ干扰素（IFN-γ）分泌增加。此外，口服或舌下免疫C3 H/HePas小鼠，这是高度敏感的C。啮齿动物感染，L. casei-Intcv诱导抗Int（cv）抗体，并显著增加攻击后的存活率。结肠切片的免疫组织化学分析显示，C。结果表明，L.干酪乳杆菌免疫的小鼠结肠切片中观察到浅表染色。casei-Intcv.结果表明，由L. casei表达intimin可能是一种有前途的方法，用C.啮齿类动物可用于评估针对EPEC的潜在疫苗。
Enteropathogenic Escherichia coli (EPEC) is a common cause of diarrhea in children from developing countries. Intimate adhesion of the bacteria to intestinal cells occurs via binding of the adhesin intimin to the TIR receptor exposed on cell surfaces. Here, Lactobacillus casei expressing a fragment of beta-intimin (L. casei-Int(cv)) was tested as mucosal vaccines in mice against intestinal colonization with the murine pathogen Citrobacter rodentium. Oral or sublingual immunization of C57BL/6 mice with L. casei-Int(cv) induced anti-Int(cv) IgA in feces but no IgG in sera. Conversely, anti-Int(cv) IgG was induced in the sera of mice after sublingual immunization with purified Int(cv). All vaccines were able to decrease C. rodentium recovery from feces. However, this reduction was more evident and sustained over time in mice immunized with L. casei-Int(cv) by the sublingual route. These mice also displayed an increase in interleukin 6 (IL-6) and gamma interferon (IFN-gamma) secretion by spleen cells 10 days after infection. Additionally, oral or sublingual immunization of C3H/HePas mice, which are highly susceptible to C. rodentium infection, with L. casei-Intcv induced anti-Int(cv) antibodies and significantly increased survival after challenge. Immunohistological analysis of colon sections revealed that C. rodentium was located in deep fractions of the tissue from C3H/HePas mice immunized with L. casei whereas superficial staining was observed in colon sections from mice immunized with L. casei-Intcv. The results indicate that vaccines composed of L. casei expressing intimin may represent a promising approach and that the C3H/HePas infection model with C. rodentium can be used to evaluate potential vaccines against EPEC.