Kinetoplastid membrane protein-11 exacerbates infection with Leishmania amazonensis in murine macrophages

Memórias do Instituto Oswaldo Cruz

Daniel Ignacchiti Lacerda²  Léa Cysne-finkelstein²  Marise Pinheiro Nunes²  Paula Mello De-luca²  Marcelo Da Silva Genestra¹  Leonor Laura Pinto Leon¹  Marcia Berrêdo-pinho¹  Leila Mendonça-lima¹  Denise Cristina De Souza Matos¹  Marco Alberto Medeiros¹  Sergio Coutinho Furtado De Mendonça² 

[1] ,Fiocruz Instituto de Tecnologia em Imunobiológicos Laboratório de ImunoparasitologiaRio de Janeiro RJ ,Brasil

关键词: kinetoplastid membrane protein-11;    Leishmania amazonensis;    macrophages;    interleukin-10;    nitric oxide;    arginase;   

DOI  :  10.1590/S0074-02762012000200014

来源: SciELO

【 摘 要 】

In Leishmania amazonensis, 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.

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