A NADPH oxidase 2 promove maior susceptibilidade à infecção por Toxoplasma gondii em camundongos

• Ano de defesa: 2019
• Autor(a) principal: Peter Silva Rocha
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Minas Gerais; Brasil; ICB - DEPARTAMENTO DE BIOQUÍMICA E IMUNOLOGIA; Programa de Pós-Graduação em Bioquímica e Imunologia; UFMG
• Palavras-chave em Português: Espécies reativas de oxigênio; Toxoplasmose; T. gondii; NADPH oxidase; Bioquímica e imunologia; Toxoplasma; Óxido nítrico; Estresse oxidativo; Resposta imune
• Link de acesso: http://hdl.handle.net/1843/45749

Toxoplasma gondii, which causes toxoplasmosis, is an obligate intracellular parasite with great ability to invade host cells and evade their defenses. Within the host, the parasite can stimulate activation of antimicrobial mechanisms, such as production of nitric oxide (NO) and reactive oxygen species (ROS). Many studies have been trying to elucidate the role of ROS during T. gondii infection, but the data are inconclusive. In order to understand the importance of ROS in T. gondii infection in vivo, we monitored for 15 days knockout mice producing NOX2 superoxide (PHOX KO) and wild type mice (C57BL/6 WT) infected with 10 cysts of T. gondii Me49 strain. (type II) intragastrically. Our results showed that WT and PHOX KO mice infected with 10 cysts of the T. gondii Me49 strain did not show mortality during the evaluated period of infection. Nevertheless, WT mice showed remarkable cachexia characteristics from the ninth day of infection, which were confirmed by high levels of pro-inflammatory cytokines (TNF and IFN-γ), NO and high weight loss compared to PHOX KO mice. We also noted that the presence of active NOX2 in T. gondii-infected WT mice promoted greater tissue damage and higher levels of inflammation in liver, which were confirmed by elevated levels of lipid peroxidation (oxidative damage) and liver enzymes (liver damage) in these mice. These data were reinforced by histopathological analysis of the liver, which showed tissue damage in WT mice at all times of infection verified by the presence of inflammatory cell infiltrate and necrosis focus. In the intestine, the parasite's main gateway to other organs, we did not observe differences in lipid peroxidation levels between groups of infected mice due to absence of parasites during the period of infection evaluated. When associating tissue damage (present in higher intensity in WT mice) with the probable production of ROS in response to infection, we did not observe differences between groups of infected mice. We also did not observe differences in the levels of antioxidant enzymes (SOD and catalase) in the liver or the intestine of the infected groups that could explain the low levels of ROS found in these mice. Our results indicate that ROS are not involved in parasite elimination during T. gondii infection. Surprisingly, oxidative stress contributes to the development of several negative consequences for the infected host, since this oxidative stress is not able to eliminate the parasite as we show in our results.