Oral Exposure to Trypanosoma cruzi Elicits a Systemic CD8+ T Cell Response and Protection against Heterotopic Challenge

Oral Exposure to Trypanosoma cruzi Elicits a Systemic CD8+ T Cell Response and Protection against Heterotopic Challenge
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DOI:
10.1128/iai.01080-10
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发表时间:
2011-08-01
影响因子:
3.1
通讯作者:
Tarleton, Rick L.
Tarleton, Rick L.
中科院分区:
医学2区
文献类型:
--
作者:
Collins, Matthew H.;Craft, Julie M.;Tarleton, Rick L.

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克氏锥虫感染了拉丁美洲数百万人,并经常导致恰加斯病的发展。克氏锥虫感染可在锥蝽病媒的叮咬部位或附近获得,但锥虫感染也是一种有充分记录的传播方式,最近因食用受寄生虫污染的食物和液体而发生的急性恰加斯病微流行证明了这一点。通过口服途径递送克氏锥虫疫苗,特别是用于免疫宿主的寄生虫活疫苗,也将是方便的。由于这些原因,我们有兴趣更好地了解口服感染或口服疫苗接种后对克氏锥虫的免疫,知道感染途径和抗原接触部位对随后的免疫反应有实质性影响。在这里,我们表明感染途径不会改变克氏T细胞在肌肉组织中建立感染的能力,也不会损害CD8(+) T细胞反应的产生。重要的是,口服减毒寄生虫疫苗可提供保护,抵御野生型克氏t型虫的攻击。这些结果有力地支持开发针对宿主物种的全生物体疫苗,作为减轻疫区恰加斯病负担的一种手段。
Trypanosoma cruzi infects millions of people in Latin America and often leads to the development of Chagas disease. T. cruzi infection can be acquired at or near the bite site of the triatomine vector, but per os infection is also a well-documented mode of transmission, as evidenced by recent microepidemics of acute Chagas disease attributed to the consumption of parasite-contaminated foods and liquids. It would also be convenient to deliver vaccines for T. cruzi by the oral route, particularly live parasite vaccines intended for the immunization of reservoir hosts. For these reasons, we were interested in better understanding immunity to T. cruzi following oral infection or oral vaccination, knowing that the route of infection and site of antigen encounter can have substantial effects on the ensuing immune response. Here, we show that the route of infection does not alter the ability of T. cruzi to establish infection in muscle tissue nor does it impair the generation of a robust CD8(+) T cell response. Importantly, oral vaccination with attenuated parasites provides protection against wild-type (WT) T. cruzi challenge. These results strongly support the development of whole-organism-based vaccines targeting reservoir species as a means to alleviate the burden of Chagas disease in affected regions.