Heme oxigenase-1 na infecção por Toxoplasma gondii: funções divergentes no controle do parasitismo in vitro e in vivo

• Ano de defesa: 2011
• Autor(a) principal: Araujo, Ester Cristina Borges
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Uberlândia; BR; Programa de Pós-graduação em Imunologia e Parasitologia Aplicadas; Ciências Biológicas; UFU
• Palavras-chave em Português: Camundongos BALB/c e C57BL/6; Citocinas; Heme oxigenase-1; Hemina; Óxido nítrico; Toxoplasma gondii; ZnPPIX; Toxoplasmose; BALB/c and C57BL/6 mice; Cytokines; Nitric oxide; Hemin; CNPQ::CIENCIAS BIOLOGICAS::IMUNOLOGIA::IMUNOLOGIA APLICADA
• Link de acesso: https://repositorio.ufu.br/handle/123456789/16675

Toxoplasma gondii is an apicomplexan parasite characterized to induce type 1 immune response in infected hosts. The parasite has a worldwide distribution and the more severe forms of the disease occur mainly in immunocompromised individuals. Heme oxygenase-1 (HO-1) is the enzyme that catabolizes free heme that induces an intense inflammatory response. Furthermore, the expression of HO-1 is induced by different stimuli, triggering an anti-inflammatory response during biological stress. In order to investigate the role of HO-1 during T. gondii infection, RAW 264.7 macrophages were infected with RH strain of T. gondii and treated with zinc protoporphyrin IX (ZnPPIX) or hemin, which inhibit or induce HO-1 expression, respectively. To verify the role of HO-1 during in vivo infection, BALB/c and C57BL/6 mice were infected with ME49 strain of T. gondii and treated with hemin or ZnPPIX during 12 days. The results showed that the inhibition of HO-1 decreased the parasitism in murine RAW 264.7 macrophages and this mechanism seems to be independent of nitric oxide (NO), since ZnPPIX treatment did not alter NO production. In addition, infected RAW 264.7 macrophages stimulated with IFN-g and treated with hemin presented an increase in NO production; on the other hand, RAW 264.7 cells treated with hemin presented higher parasite replication in comparison with non-treated ones. During in vivo infection, we observed that the activity of HO-1 did not alter the inflammatory changes in the organs of T. gondii infected BALB/c and C57BL/6 mice. Interestingly, both mice lineages treated with ZnPPIX showed higher parasitism in the lung, whereas treatment with hemin decreased the replication of the parasite in the lung and small intestine of C57BL/6. The levels of IFN-g, TNF, TGF-b and IL-10 in the sera of infected animals were not altered with the inhibition or induction of HO-1 activity. In conclusion, our data suggest that the increased HO-1 activity is important to decrease T. gondii replication in the lung and small intestine, although the mechanisms involved need to be elucidated. Additionally, the mechanisms mediated by HO-1 in T. gondii infection are different in vitro and in vivo, since the increased HO-1 activity enhances the parasite multiplication in vitro.