de Souza E M, Araújo-Jorge T C, Bailly C, Lansiaux A, Batista M M, Oliveira G M, Soeiro M N C
Lab. Biologia Celular, DUBC, FIOCRUZ, Instituto Oswaldo Cruz, Avenida Brasil 4365, Manguinhos, 21045-900, Rio de Janeiro, Brazil.
Cell Tissue Res. 2003 Nov;314(2):223-35. doi: 10.1007/s00441-003-0782-5. Epub 2003 Aug 20.
The mechanism of cell death which occurs during Chagas' cardiopathy is disputed. To address this issue we analyzed the molecular pathways implicated in the death of cardiomyocytes during T. cruzi invasion and found that they undergo apoptosis during both in vitro and in vivo infections. However, the death rates and onset were related to the parasite stocks belonging to different biodemes, which can be correlated to the different histological inflammation findings that have already been reported. Our in vitro data provide additional support for this hypothesis since higher levels and earlier apoptosis induction were noted during the interaction with the Dm28c (type I) as compared to the Y and CL stocks (type II). Modifications of the surface carbohydrates of the infected cardiomyocytes were observed and these molecular events may be acting as "eat me" tags for their final engulfment by macrophages and/or other non-professional phagocytes. The analysis of other host cell types showed that the in vitro infection of fibroblasts did not result in host apoptosis even when a highly infective stock was used. Conversely, infected macrophages undergo apoptosis but at a higher degree than cardiomyocytes. Apoptotic intracellular parasites were observed to varied extents depending on the T. cruzi stock, which was related to the parasite invasion and proliferation. In summary, our results show that during T. cruzi infection, the extent of apoptosis varies according to the host cell type and the parasite stocks. The apoptosis of both host and T. cruzi can contribute to the silent spreading and persistence of the parasite without triggering an exacerbated inflammatory response.
恰加斯心肌病期间发生的细胞死亡机制存在争议。为解决这一问题，我们分析了克氏锥虫入侵期间心肌细胞死亡所涉及的分子途径，发现它们在体外和体内感染过程中均会发生凋亡。然而，死亡率和发病时间与属于不同生物型的寄生虫株有关，这与已报道的不同组织学炎症结果相关。我们的体外数据为这一假设提供了额外支持，因为与Y和CL株（II型）相比，在与Dm28c（I型）相互作用期间，观察到更高水平和更早的凋亡诱导。观察到受感染心肌细胞表面碳水化合物的修饰，这些分子事件可能作为“吃我”信号，最终被巨噬细胞和/或其他非专职吞噬细胞吞噬。对其他宿主细胞类型的分析表明，即使使用高感染性株，成纤维细胞的体外感染也不会导致宿主凋亡。相反，受感染的巨噬细胞会发生凋亡，但程度高于心肌细胞。根据克氏锥虫株的不同，观察到凋亡的细胞内寄生虫程度不同，这与寄生虫的入侵和增殖有关。总之，我们的结果表明，在克氏锥虫感染期间，凋亡程度根据宿主细胞类型和寄生虫株而有所不同。宿主和克氏锥虫的凋亡都可能导致寄生虫的无声传播和持续存在，而不会引发加剧的炎症反应。
