Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Microbes Infect. 2010 Aug;12(8-9):669-76. doi: 10.1016/j.micinf.2010.04.011. Epub 2010 May 7.
Chagas' disease is caused by Trypanosoma cruzi infection and is characterized by chronic fibrogenic inflammation and heart dysfunction. Chemokines are produced during infection and drive tissue inflammation. In rats, acute infection is characterized by intense myocarditis and regression of inflammation after control of parasitism. We investigated the role of CCL3 and CCL5 during infection by using DNA vaccination encoding for each chemokine separately or simultaneously. MetRANTES treatment was used to evaluate the role of CCR1 and CCR5, the receptors for CCL3 and CCL5. Vaccination with CCL3 or CCL5 increased heart parasitism and decreased local IFN-gamma production, but did not influence intensity of inflammation. Simultaneous treatment with both plasmids or treatment with MetRANTES enhanced cardiac inflammation, fibrosis and parasitism. In conclusion, chemokines CCL3 and CCL5 are relevant, but not essential, for control of T. cruzi infection in rats. On the other hand, combined blockade of these chemokines or their receptors enhanced tissue inflammation and fibrosis, clearly contrasting with available data in murine models of T. cruzi infection. These data reinforce the important role of chemokines during T. cruzi infection but suggest that caution must be taken when expanding the therapeutic modulation of the chemokine system in mice to the human infection.
恰加斯病是由克氏锥虫感染引起的，其特征为慢性纤维性炎症和心脏功能障碍。趋化因子在感染过程中产生，并驱动组织炎症。在大鼠中，急性感染的特征为剧烈的心肌炎，寄生虫得到控制后炎症消退。我们通过单独或同时对每种趋化因子进行 DNA 疫苗接种，研究了趋化因子 CCL3 和 CCL5 在感染过程中的作用。使用 MetRANTES 治疗来评估 CCR1 和 CCR5（CCL3 和 CCL5 的受体）的作用。CCL3 或 CCL5 的疫苗接种增加了心脏寄生虫感染，并减少了局部 IFN-γ的产生，但不影响炎症的强度。同时用两种质粒治疗或用 MetRANTES 治疗增强了心脏炎症、纤维化和寄生虫感染。总之，趋化因子 CCL3 和 CCL5 对于控制大鼠中的 T. cruzi 感染是相关的，但不是必需的。另一方面，联合阻断这些趋化因子或其受体增强了组织炎症和纤维化，这与 T. cruzi 感染的小鼠模型中的现有数据明显相反。这些数据强化了趋化因子在 T. cruzi 感染过程中的重要作用，但表明在将趋化因子系统的治疗调节从小鼠扩展到人类感染时必须谨慎。
