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Mem. Inst. Oswaldo Cruz ; 107(2): 238-245, Mar. 2012. ilus, graf
Artigo em Inglês | LILACS | ID: lil-617071

RESUMO

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.


Assuntos
Animais , Feminino , Camundongos , Arginase/metabolismo , /imunologia , Leishmania mexicana/efeitos dos fármacos , Macrófagos Peritoneais/parasitologia , Proteínas de Membrana/farmacologia , Óxido Nítrico/biossíntese , Proteínas de Protozoários/farmacologia , Células Cultivadas , Leishmania mexicana/imunologia , Camundongos Endogâmicos BALB C , Macrófagos Peritoneais/enzimologia , Macrófagos Peritoneais/imunologia
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