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.
