Kinetoplastid membrane protein-11 exacerbates infection with Leishmania amazonensis in murine macrophages
Mem. Inst. Oswaldo Cruz
;
107(2): 238-245, Mar. 2012. ilus, graf
Artículo
en Inglés
| LILACS
| ID: lil-617071
ABSTRACT
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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LILACS (Américas)
Asunto principal:
Arginasa
/
Leishmania mexicana
/
Proteínas Protozoarias
/
Macrófagos Peritoneales
/
Proteínas de la Membrana
/
Óxido Nítrico
Límite:
Animales
Idioma:
Inglés
Revista:
Mem. Inst. Oswaldo Cruz
Asunto de la revista:
Medicina Tropical
/
Parasitología
Año:
2012
Tipo del documento:
Artículo
País de afiliación:
Brasil
Institución/País de afiliación:
Fiocruz/BR
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