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Memórias do Instituto Oswaldo Cruz
Fundação Oswaldo Cruz, Fiocruz
ISSN: 1678-8060
EISSN: 1678-8060
Vol. 107, No. 2, 2012, pp. 238-245
Bioline Code: oc12035
Full paper language: English
Document type: Research Article
Document available free of charge

Memórias do Instituto Oswaldo Cruz, Vol. 107, No. 2, 2012, pp. 238-245

 en Kinetoplastid membrane protein-11 exacerbates infection with Leishmania amazonensis check for this species in other resources in murine macrophages
Lacerda, Daniel Ignacchiti; Cysne-Finkelstein, Léa; Nunes, Marise Pinheiro; De-Luca, Paula Mello; Genestra, Marcelo da Silva; Leon, Leonor Laura Pinto; Berrêdo-Pinho, Marcia; Mendonça-Lima, Leila; Matos, Denise Cristina de Souza; Medeiros, Marco Alberto & de Mendonça, Sergio Coutinho Furtado

Abstract

In Leishmania amazonensis check for this species in other resources , kinetoplastid membrane protein-11 (KMP-11) expression increases during metacyclogenesis and is higher in amastigotes than in promastigotes, suggesting a role for this protein in the infection of the mammalian host. We show that the addition of KMP-11 exacerbates L. amazonensis infection in peritoneal macrophages from BALB/c mice by increasing interleukin (IL)-10 secretion and arginase activity while reducing nitric oxide (NO) production. The doses of KMP-11, the IL-10 levels and the intracellular amastigote loads were strongly, positively and significantly correlated. The increase in parasite load induced by KMP-11 was inhibited by anti-KMP-11 or anti-IL-10 neutralising antibodies, but not by isotype controls. The neutralising antibodies, but not the isotype controls, were also able to significantly decrease the parasite load in macrophages cultured without the addition of KMP-11, demonstrating that KMP-11-induced exacerbation of the infection is not dependent on the addition of exogenous KMP-11 and that the protein naturally expressed by the parasite is able to promote it. In this study, the exacerbating effect of KMP-11 on macrophage infection with Leishmania is for the first time demonstrated, implicating it as a virulence factor in L. amazonensis. The stimulation of IL-10 production and arginase activity and the inhibition of NO synthesis are likely involved in this effect.

Keywords
kinetoplastid membrane protein-11 - Leishmania amazonensis - macrophages - interleukin-10 - nitric oxide - arginase

 
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