Distinct populations of Trypanosoma cruzi interact with mammalian cardiac muscle cells causing different inflammation patterns and low heart functionality. During T. cruzi infection, the extracellular ATP is hydrolyzed to tri- and/or diphosphate nucleotides, based on the infectivity, virulence, and regulation of the inflammatory response. T. cruzi carries out this hydrolysis through the T. cruzi ectonucleotidase, NTPDase-1 (TcNTPDase-1). This study aimed to evaluate the role of TcNTPDase-1 in culture rich in metacyclic trypomastigote forms (MT) and cell culture-derived trypomastigote forms (CT) from Colombiana (discrete typing unit - DTU I), VL-10 (DTU II), and CL (DTU VI) strains of T. cruzi. For this, we measured TcNTPDase-1 activity in suramin-treated and untreated parasites and infected J774 cells and C57BL/6 mice with suramin pre-treated parasites to assess parasitic and inflammatory cardiac profile in the acute phase of infection. Our data indicated a higher TcNTPDase-1 activity for ATP in culture rich in metacyclic trypomastigote forms from Colombiana strain in comparison to those from VL-10 and CL strains. The cell culture-derived trypomastigote forms from CL strain presented higher capacity to hydrolyze ATP than those from Colombiana and VL-10 strains. Suramin inhibited ATP hydrolysis in all studied parasite forms and strains. Suramin pre-treated parasites reduced J774 cell infection and increased nitrite production in vitro. In vivo studies showed a reduction of inflammatory infiltrate in the cardiac tissues of animals infected with cell culture-derived trypomastigote forms from suramin pre-treated Colombiana strain. In conclusion, TcNTPDase-1 activity in trypomastigotes forms drives part of the biological characteristics observed in distinct DTUs and may induce cardiac pathogenesis during T. cruzi infection.

中文翻译：

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来自不同来源和不同遗传背景的锥虫的外核苷酸酶增强了它们的传染性和宿主炎症

克氏锥虫的不同种群与哺乳动物心肌细胞相互作用，导致不同的炎症模式和低心脏功能。在 T. cruzi 感染期间，根据感染性、毒力和炎症反应的调节，细胞外 ATP 被水解为三磷酸和/或二磷酸核苷酸。T. cruzi 通过 T. cruzi 外核苷酸酶 NTPDase-1 (TcNTPDase-1) 进行这种水解。本研究旨在评估 TcNTPDase-1 在来自哥伦比亚（离散分型单元 - DTU I）、VL-10 (DTU II)、富含亚环鞭毛体形式 (MT) 和细胞培养衍生的锥鞭毛体形式 (CT) 的培养物中的作用，和 T. cruzi 的 CL (DTU VI) 菌株。为了这，我们测量了苏拉明处理和未处理的寄生虫以及感染的 J774 细胞和 C57BL/6 小鼠中的 TcNTPDase-1 活性，以评估感染急性期的寄生虫和炎症心脏特征。我们的数据表明，与来自 VL-10 和 CL 菌株的那些相比，来自哥伦比亚菌株的富含亚环锥鞭毛体形式的培养物中 ATP 的 TcNTPDase-1 活性更高。来自 CL 菌株的细胞培养衍生的锥鞭毛体形式比来自 Columbiana 和 VL-10 菌株的那些具有更高的水解 ATP 的能力。苏拉明抑制了所有研究的寄生虫形式和菌株中的 ATP 水解。苏拉明预处理的寄生虫减少了 J774 细胞感染并增加了体外亚硝酸盐的产生。体内研究表明，感染了来自苏拉明预处理的哥伦比亚菌株的细胞培养衍生的锥鞭毛体形式的动物心脏组织中的炎症浸润减少。总之，锥鞭毛体形式中的 TcNTPDase-1 活性驱动了在不同 DTU 中观察到的部分生物学特征，并可能在 T. cruzi 感染期间诱发心脏发病机制。