Basso Beatriz
Beatriz Basso, Neonatology Service, School of Medical Sciences, National University of Cordoba, 5000 Cordoba, Argentina.
World J Exp Med. 2013 Feb 20;3(1):1-10. doi: 10.5493/wjem.v3.i1.1.
Trypanosoma cruzi (T. cruzi), the etiological agent of Chagas disease, affects nearly 18 million people in Latin America and 90 million are at risk of infection. The parasite presents two stages of medical importance in the host, the amastigote, intracellular replicating form, and the extracellular trypomastigote, the infective form. Thus infection by T. cruzi induces a complex immune response that involves effectors and regulatory mechanisms. That is why control of the infection requires a strong humoral and cellular immune response; hence, the outcome of host-parasite interaction in the early stages of infection is extremely important. A critical event during this period of the infection is innate immune response, in which the macrophage's role is vital. Thus, after being phagocytized, the parasite is able to develop intracellularly; however, during later periods, these cells induce its elimination by means of toxic metabolites. In turn, as the infection progresses, adaptive immune response mechanisms are triggered through the TH1 and TH2 responses. Finally, T. cruzi, like other protozoa such as Leishmania and Toxoplasma, have numerous evasive mechanisms to the immune response that make it possible to spread around the host. In our Laboratory we have developed a vaccination model in mice with Trypanosoma rangeli, nonpathogenic to humans, which modulates the immune response to infection by T. cruzi, thus protecting them. Vaccinated animals showed an important innate response (modulation of NO and other metabolites, cytokines, activation of macrophages), a strong adaptive cellular response and significant increase in specific antibodies. The modulation caused early elimination of the parasites, low parasitaemia, the absence of histological lesions and high survival rates. Even though progress has been made in the knowledge of some of these mechanisms, new studies must be conducted which could target further prophylactic and therapeutic trials against T. cruzi infection.
克氏锥虫是恰加斯病的病原体，在拉丁美洲感染了近1800万人，另有9000万人面临感染风险。该寄生虫在宿主体内呈现出两个具有医学重要性的阶段，即无鞭毛体（细胞内复制形式）和细胞外锥鞭毛体（感染形式）。因此，克氏锥虫感染会引发复杂的免疫反应，涉及效应器和调节机制。这就是为什么控制感染需要强大的体液免疫和细胞免疫反应；因此，宿主与寄生虫在感染早期相互作用的结果极为重要。感染期间的一个关键事件是先天性免疫反应，其中巨噬细胞的作用至关重要。因此，寄生虫被吞噬后能够在细胞内发育；然而，在后期，这些细胞会通过有毒代谢产物诱导其被清除。反过来，随着感染的进展，适应性免疫反应机制通过TH1和TH2反应被触发。最后，克氏锥虫与利什曼原虫和弓形虫等其他原生动物一样，有许多逃避免疫反应的机制，使其能够在宿主体内传播。在我们实验室，我们用对人类无致病性的兰氏锥虫在小鼠中开发了一种疫苗接种模型，该模型可调节对克氏锥虫感染的免疫反应，从而保护小鼠。接种疫苗的动物表现出重要的先天性反应（一氧化氮和其他代谢产物、细胞因子的调节，巨噬细胞的激活）、强烈的适应性细胞反应以及特异性抗体的显著增加。这种调节导致寄生虫早期清除、低寄生虫血症、无组织学损伤和高存活率。尽管在了解其中一些机制方面取得了进展，但仍必须进行新的研究，这些研究可能针对针对克氏锥虫感染的进一步预防和治疗试验。
