Laboratório de Immunopatologia, Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, MG, Brazil.
Expert Rev Mol Med. 2010 Sep 15;12:e29. doi: 10.1017/S1462399410001560.
Infection with the protozoan parasite Trypanosoma cruzi, the agent of Chagas disease, is characterised by a variable clinical course - from symptomless cases to severe chronic disease with cardiac and/or gastrointestinal involvement. The variability in disease outcome has been attributed to host responses as well as parasite heterogeneity. In this article, we review studies indicating the importance of immune responses as key determinants of host resistance to T. cruzi infection and the pathogenesis of Chagas disease. Particular attention is given to recent studies defining the role of cognate innate immune receptors and immunodominant CD8+ T cells that recognise parasite components - both crucial for host-parasite interaction and disease outcome. In light of these studies we speculate about parasite strategies that induce a strong and long-lasting T-cell-mediated immunity but at the same time allow persistence of the parasite in the vertebrate host. We also discuss what we have learned from these studies for increasing our understanding of Chagas pathogenesis and for the design of new strategies to prevent the development of Chagas disease. Finally, we highlight recent studies employing a genetically engineered attenuated T. cruzi strain as a vaccine shuttle that elicits potent T cell responses specific to a tumour antigen and protective immunity against a syngeneic melanoma cell line.
感染原生动物寄生虫克氏锥虫，恰加斯病的病原体，其临床过程具有多变性——从无症状病例到严重的慢性疾病，伴有心脏和/或胃肠道受累。疾病结局的可变性归因于宿主反应和寄生虫异质性。在本文中，我们回顾了表明免疫反应作为宿主抵抗克氏锥虫感染和恰加斯病发病机制的关键决定因素的重要性的研究。特别关注最近的研究，这些研究定义了识别寄生虫成分的同源先天免疫受体和免疫优势 CD8+T 细胞的作用——这两者对于宿主-寄生虫相互作用和疾病结局都是至关重要的。鉴于这些研究，我们推测寄生虫诱导强烈和持久的 T 细胞介导免疫的策略，但同时允许寄生虫在脊椎动物宿主中持续存在。我们还讨论了我们从这些研究中学到的东西，以增加我们对恰加斯病发病机制的理解，并设计新的策略来预防恰加斯病的发展。最后，我们强调了最近的研究，这些研究使用基因工程减毒克氏锥虫菌株作为疫苗穿梭物，引发针对肿瘤抗原的强烈 T 细胞反应和对同源黑色素瘤细胞系的保护性免疫。
