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The role of heme oxygenase-1 on canine visceral leishmaniasis

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Author(s):
Breno Fernando Martins de Almeida
Total Authors: 1
Document type: Doctoral Thesis
Press: Araçatuba. 2016-08-26.
Institution: Universidade Estadual Paulista (Unesp). Faculdade de Medicina Veterinária. Araçatuba
Defense date:
Advisor: Valéria Marçal Felix de Lima; Paulo César Ciarlini
Abstract

Canine visceral leishmaniasis (CVL) is a chronic disease that causes immunosuppression by reducing the cellular response of infected animals, impairing the cell proliferation and the phagocytic ability of defense cells. Recently, heme oxygenase-1 (HO-1) has been highlighted for being involved in regulation of cell response in certain pathological conditions, and for being an enzyme that can be induced by stress conditions, such as oxidative stress, that is known to occur in CVL. In this context, this study aimed to determine the role of HO-1 in CVL, determining its levels and expression in infected and healthy dogs, correlating these findings with oxidative stress, parasite load and IL-10. The effect of induction and inhibition of HO-1 on lymphoproliferative response by lymph node cells of infected dogs and macrophage infection rate by promastigotes of Leishmania infantum were also evaluated. Dogs with CVL showed marked oxidative stress and increased levels and expression of HO-1, obtaining a positive correlation between HO-1 and oxidative stress and IL-10 in a tissue-dependent way. Inhibition of HO-1 increased proliferation rate in the presence of L. infantum soluble antigen, while induction of HO-1 decreased antigen-specific proliferation and increased macrophage infection rate and number of amastigotes per macrophage. The increase in HO-1 metabolism observed in CVL is associated to oxidative stress present in these dogs and could be one of the mechanisms involved in the inhibition of the lymphoproliferative response, permitting the perpetuation of infection by the inhibition of macrophage microbicidal activity. (AU)

FAPESP's process: 13/06068-6 - The role of heme oxygenase-1 on canine visceral leishmaniasis
Grantee:Breno Fernando Martins de Almeida
Support Opportunities: Scholarships in Brazil - Doctorate