Ectonucleotidases from trypomastigotes from different sources and various genetic backgrounds of Trypanosoma cruzi potentiate their infectivity and host inflammation

Cytokine. 2020 Dec:136:155255. doi: 10.1016/j.cyto.2020.155255. Epub 2020 Aug 28.

Abstract

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.

Keywords: ATP; Ectonucleotidase; Inflammation; Suramin; Trypanosoma cruzi; Trypomastigotes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD* / genetics
  • Antigens, CD* / metabolism
  • Apyrase* / genetics
  • Apyrase* / metabolism
  • Cell Line, Tumor
  • Chagas Disease* / enzymology
  • Chagas Disease* / genetics
  • Mice
  • Mice, Inbred BALB C
  • Protozoan Proteins* / genetics
  • Protozoan Proteins* / metabolism
  • Species Specificity
  • Trypanosoma cruzi* / enzymology
  • Trypanosoma cruzi* / genetics
  • Trypanosoma cruzi* / pathogenicity
  • Virulence Factors* / genetics
  • Virulence Factors* / metabolism

Substances

  • Antigens, CD
  • Protozoan Proteins
  • Virulence Factors
  • Apyrase
  • CD39 antigen