Nascentes Gabriel Antonio Nogueira, Hernández César Gómez, Rabelo Rosiley Aparecida de Souza, Coelho Raquel Fernandes, Morais Fabiana Rossetto de, Marques Tatiane, Batista Lara Rocha, Meira Wendell Sérgio Ferreira, Oliveira Carlo José Freire de, Lages Silva Eliane, Ramírez Luis Eduardo
1 Microbiology and Immunology Discipline, Federal Institute of Education , Science and Technology at Triângulo Mineiro (IFTM), Uberaba, Brazil .
2 Department of Microbiology, Immunology and Parasitology, Institute of Biological and Natural Sciences, Federal University of Triângulo Mineiro (UFTM) , Uberaba, Brazil .
Vector Borne Zoonotic Dis. 2016 May;16(5):317-25. doi: 10.1089/vbz.2015.1874. Epub 2016 Mar 9.
In previous studies, we have demonstrated that inoculation with a Trypanosoma cruzi marinkellei (avirulent RM1 strain) was able to reduce parasitemia in mice challenged with T. cruzi, although it was not able to prevent histopathological lesions. Th1 response stimulation by immunization is necessary for T. cruzi infection control, but the resistance is also dependent on immunoregulatory mechanisms, which can be induced by adjuvants. Thus, we evaluated whether inoculation of T. cruzi marinkellei associated with administration of different adjuvants would be capable of inducing different patterns of immune response to maximize the immune response against T. cruzi (virulent Romildo strain) infection. Two hundred eighty nonisogenic mice were divided into 14 groups according to the immunization scheme and the subsequent challenge with virulent Romildo T. cruzi strain. Nonimmunized groups and animals inoculated without adjuvants were also included. Immune protection was not observed with Th2 adjuvants (incomplete Freund's adjuvant [IFA] and Alum) due to high parasitemia. Th1/Th2-polarizing adjuvants also did not induce immune protection because inulin was unable to maintain survival, and immune-stimulating complexes induced intense inflammatory processes. Animals sensitized with RM1 strain without adjuvants were able to reduce parasitemia, increase survival, and protect against severe histological lesions, followed by adequate cytokine stimulation. Finally, our results demonstrate that the early and balanced IFN-γ production becomes critical to promote protection and that Th1 adjuvant elicited a controversial infection control due to increased histopathological damage. Therefore, the host's immunomodulation remains one of the most important challenges in the research for effective protection against T. cruzi infection. Similarly, the identification of protective antigens in the RM1 strain of T. cruzi marinkellei may contribute to further studies on vaccine development against human Chagas disease.
在先前的研究中，我们已经证明，用克氏锥虫马林凯雷株（无毒RM1株）接种能够降低受到克氏锥虫攻击的小鼠的寄生虫血症，尽管它无法预防组织病理学损伤。免疫刺激Th1反应对于控制克氏锥虫感染是必要的，但抵抗力也取决于免疫调节机制，而免疫调节机制可由佐剂诱导。因此，我们评估了接种克氏锥虫马林凯雷株并给予不同佐剂是否能够诱导不同的免疫反应模式，以最大限度地增强针对克氏锥虫（有毒罗米尔多株）感染的免疫反应。根据免疫方案和随后用有毒的罗米尔多克氏锥虫株进行攻击，将280只非同源小鼠分为14组。还包括未免疫组和未使用佐剂接种的动物。由于寄生虫血症高，Th2佐剂（不完全弗氏佐剂[IFA]和明矾）未观察到免疫保护作用。Th1/Th2极化佐剂也未诱导免疫保护，因为菊粉无法维持生存率，且免疫刺激复合物会引发强烈的炎症过程。用RM1株无佐剂致敏的动物能够降低寄生虫血症、提高生存率并预防严重的组织学损伤，随后有适当的细胞因子刺激。最后，我们的结果表明，早期且平衡的IFN-γ产生对于促进保护至关重要，并且Th1佐剂由于组织病理学损伤增加而引发了有争议的感染控制。因此，宿主的免疫调节仍然是有效预防克氏锥虫感染研究中最重要的挑战之一。同样，鉴定克氏锥虫马林凯雷株RM1中的保护性抗原可能有助于进一步开展针对人类恰加斯病疫苗开发的研究。
