Distinct Trypanosoma cruzi isolates induce activation and apoptosis of human neutrophils

Abstract

Neutrophils are critical players in the first line of defense against pathogens and in the activation of subsequent cellular responses. We aimed to determine the effects of the interaction of Trypanosoma cruzi with human neutrophils, using isolates of the two major discrete type units (DTUs) associated with Chagas’ disease in Latin America (clone Col1.7G2 and Y strain, DTU I and II, respectively). Thus, we used CFSE-stained trypomastigotes to measure neutrophil-T. cruzi interaction, neutrophil activation, cytokine expression and death, after infection with Col1.7G2 and Y strain. Our results show that the frequency of CFSE+ neutrophils, indicative of interaction, and CFSE intensity on a cell-per-cell basis were similar when comparing Col1.7G2 and Y strains. Interaction with T. cruzi increased neutrophil activation, as measured by CD282, CD284, TNF and IL-12 expression, although at different levels between the two strains. No change in IL-10 expression was observed after interaction of neutrophils with either strain. We observed that exposure to Y and Col1.7G2 caused marked neutrophil death. This was specific to neutrophils, since interaction of either strain with monocytes did not cause death. Our further analysis showed that neutrophil death was a result of apoptosis, which was associated with an upregulation of TNF-receptor, TNF and FasLigand, but not of Fas. Induction of TNF-associated neutrophil apoptosis by the different T. cruzi isolates may act as an effective common mechanism to decrease the host’s immune response and favor parasite survival.

Co‐infection with distinct Trypanosoma cruzi strains induces an activated immune response in human monocytes

“…In fact, the decrease in infected cells was also accompanied by a decrease in TNF + cells, suggesting that these cells may undergo apoptosis, as previous studies have shown that TNF can induce apoptosis . We have also shown that T cruzi infection induces apoptosis in neutrophils, which is associated with TNF production . In addition to this hypothesis, it is also possible that heavily infected cells are dying due to parasite‐induced rupture.…”

“…Initial contact of immune cells with the parasite is critical for shaping the subsequent adaptive response during infection, and we have previously shown that the initial contact with different T cruzi strains can interfere with monocyte and neutrophil immune profiles . We hypothesize that two strains from different DTUs, associated with mild or severe clinical manifestations of Chagas disease, induce different immune responses in human monocytes and may influence one another during co‐infection.…”

Lipid Bodies as Sites of Prostaglandin E2 Synthesis During Chagas Disease: Impact in the Parasite Escape Mechanism

“…During T. cruzi infection, the induction of apoptosis, especially of T and B lymphocytes ( Freire-de-Lima et al, 2000 ; DosReis, 2011 ) and neutrophils ( Magalhaes et al, 2017 ) represents an important mechanism that contributes to the parasite replication, due to the immunomodulatory effects on the host immune response ( Decote-Ricardo et al, 2017 ). Consequently, the efferocytosis or phagocytic clearance of these apoptotic cells by macrophages has profound consequences on innate and adaptive immune responses in inflamed tissues ( Elliott et al, 2017 ).…”

Involvement of neutrophils in Chagas disease pathology

“…Neutrophils can modulate T cruzi infection due to apoptosis; human neutrophils when stimulated with different strains of the parasite are activated and enter apoptosis. 59 These in vitro data suggest that neutrophils may play a role in the regulation of T cruzi infection.…”

“…These observations show that resistance or susceptibility to infection in both animal models is the result of participation of neutrophils, not excluding other mechanisms that may be involved in this process. Neutrophils can modulate T cruzi infection due to apoptosis; human neutrophils when stimulated with different strains of the parasite are activated and enter apoptosis . These in vitro data suggest that neutrophils may play a role in the regulation of T cruzi infection.…”