Kinetoplastid membrane protein-11 exacerbates infection with Leishmania amazonensis in murine macrophages
Mem. Inst. Oswaldo Cruz
;
107(2): 238-245, Mar. 2012. ilus, graf
Article
in English
| 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.
Full text:
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Index:
LILACS (Americas)
Main subject:
Arginase
/
Leishmania mexicana
/
Protozoan Proteins
/
Macrophages, Peritoneal
/
Membrane Proteins
/
Nitric Oxide
Limits:
Animals
Language:
English
Journal:
Mem. Inst. Oswaldo Cruz
Journal subject:
Tropical Medicine
/
Parasitology
Year:
2012
Type:
Article
Affiliation country:
Brazil
Institution/Affiliation country:
Fiocruz/BR
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