Avaliação do papel de ambientes oxidantes intracelulares no perfil de multiplicação intracelular de T. cruzi: meta-análise

Abstract

Chagas disease is a neglected malady caused by the protozoan Trypanosoma cruzi. This organism infects invertebrate and vertebrate hosts, in which it faces several challenges for survival and proliferation. In mammals, the infection leads to cell oxidative responses generating reactive oxygen species (ROS). Scientific literature demonstrates that the effects of ROS can be both harmful and beneficial to T. cruzi, leading to cell death mechanisms or promoting its multiplication. The reasons for those differences are not well understood, but data show that strains belonging to different discrete typing units (DTUs) respond differently to these stimuli. Thus, we sought, by grouping studies in a systematic review with meta-analysis, to obtain information about the influence of oxidizing or reducing intracellular environments on the rate of T. cruzi amastigote replication, focusing on strains belonging to DTUs I and II. The research was conducted in PubMed and Embase, in September 6th, 2020, without language restrictions and not including secondary or ‘grey literature’ (reviews, editorials, congress abstracts, thesis, dissertations). The search strategy was built determining population (Trypanosoma cruzi) and intervention (ROS) with controlled vocabulary (MesH, Emtree), title, title and abstract and free terms. 1109 references were recovered. They were screened to remove duplicates and by analysis of title, title and abstract, as well as methodology with help of inclusion and exclusion criteria, defined a priori. A list with eligible studies was obtained and eight of them were randomly selected by means of an online tool for generation of random numbers, to minimize bias in the selection process. The papers included in the meta-analysis were heterogeneous, gathering data from several parasite strains, techniques for assessing T. cruzi burden, as well as cell and animal lineages, reflected in the statistical data, I-squared test of heterogeneity. After the meta-analysis was performed, it was not possible to identify a DTU-specific profile for intracellular multiplication. Besides the heterogeneity in the papers, we highlight the existence of very few studies evaluating the effect of oxidative stress on the intracellular proliferation, indicating the need for further experimental investigation in this area.