| First Author | Prolo C | Year | 2021 |
| Journal | Redox Biol | Volume | 46 |
| Pages | 102085 | PubMed ID | 34454164 |
| Mgi Jnum | J:350398 | Mgi Id | MGI:6766178 |
| Doi | 10.1016/j.redox.2021.102085 | Citation | Prolo C, et al. (2021) Nox2-derived superoxide radical is crucial to control acute Trypanosoma cruzi infection. Redox Biol 46:102085 |
| abstractText | Trypanosoma cruzi is a flagellated protozoan that undergoes a complex life cycle between hematophagous insects and mammals. In humans, this parasite causes Chagas disease, which in thirty percent of those infected, would result in serious chronic pathologies and even death. Macrophages participate in the first stages of infection, mounting a cytotoxic response which promotes massive oxidative damage to the parasite. On the other hand, T. cruzi is equipped with a robust antioxidant system to repeal the oxidative attack from macrophages. This work was conceived to explicitly assess the role of mammalian cell-derived superoxide radical in a murine model of acute infection by T. cruzi. Macrophages derived from Nox2-deficient (gp91(phox)-/-) mice produced marginal amounts of superoxide radical and were more susceptible to parasite infection than those derived from wild type (wt) animals. Also, the lack of superoxide radical led to an impairment of parasite differentiation inside gp91(phox)-/- macrophages. Biochemical or genetic reconstitution of intraphagosomal superoxide radical formation in gp91(phox)-/- macrophages reverted the lack of control of infection. Along the same line, gp91(phox)-/- infected mice died shortly after infection. In spite of the higher lethality, parasitemia did not differ between gp91(phox)-/- and wt animals, recapitulating an observation that has led to conflicting interpretations about the importance of the mammalian oxidative response against T. cruzi. Importantly, gp91(phox)-/- mice presented higher and disseminated tissue parasitism, as evaluated by both qPCR- and bioimaging-based methodologies. Thus, this work supports that Nox2-derived superoxide radical plays a crucial role to control T. cruzi infection in the early phase of a murine model of Chagas disease. |
