Bustamante Juan, Tarleton Rick
Centro de Investigación en Salud Internacional de Barcelona, Hospital Clínic, Universitat de Barcelona, Barcelona, Spain.
Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, GA, USA.
Mem Inst Oswaldo Cruz. 2015 May;110(3):445-51. doi: 10.1590/0074-02760140440. Epub 2015 Apr 28.
Prevention of Trypanosoma cruzi infection in mammals likely depends on either prevention of the invading trypomastigotes from infecting host cells or the rapid recognition and killing of the newly infected cells by T. cruzi-specific T cells. We show here that multiple rounds of infection and cure (by drug therapy) fails to protect mice from reinfection, despite the generation of potent T cell responses. This disappointing result is similar to that obtained with many other vaccine protocols used in attempts to protect animals from T. cruzi infection. We have previously shown that immune recognition of T. cruzi infection is significantly delayed both at the systemic level and at the level of the infected host cell. The systemic delay appears to be the result of a stealth infection process that fails to trigger substantial innate recognition mechanisms while the delay at the cellular level is related to the immunodominance of highly variable gene family proteins, in particular those of the trans-sialidase family. Here we discuss how these previous studies and the new findings herein impact our thoughts on the potential of prophylactic vaccination to serve a productive role in the prevention of T. cruzi infection and Chagas disease.
预防哺乳动物感染克氏锥虫可能取决于防止入侵的锥鞭毛体感染宿主细胞，或者取决于克氏锥虫特异性T细胞对新感染细胞的快速识别和杀伤。我们在此表明，尽管产生了有效的T细胞反应，但多轮感染和（药物治疗）治愈并不能保护小鼠免受再次感染。这一令人失望的结果与许多其他用于试图保护动物免受克氏锥虫感染的疫苗方案所得到的结果相似。我们之前已经表明，克氏锥虫感染的免疫识别在全身水平和受感染宿主细胞水平均显著延迟。全身延迟似乎是一种隐匿感染过程的结果，该过程未能触发大量的天然识别机制，而细胞水平的延迟与高度可变基因家族蛋白（特别是转唾液酸酶家族蛋白）的免疫显性有关。在此，我们讨论这些先前的研究以及本文中的新发现如何影响我们对于预防性疫苗接种在预防克氏锥虫感染和恰加斯病中发挥有效作用的潜力的看法。
