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

摘要

In Leishmania amazonensis , kinetoplastid membrane protein-11 (KMP-11) expression increases during metacyclogenesisand is higher in amastigotes than in promastigotes, suggesting a role for this protein in the infectionof the mammalian host. We show that the addition of KMP-11 exacerbates L. amazonensis infection in peritonealmacrophages from BALB/c mice by increasing interleukin (IL)-10 secretion and arginase activity while reducingnitric oxide (NO) production. The doses of KMP-11, the IL-10 levels and the intracellular amastigote loads werestrongly, positively and significantly correlated. The increase in parasite load induced by KMP-11 was inhibited byanti-KMP-11 or anti-IL-10 neutralising antibodies, but not by isotype controls. The neutralising antibodies, but notthe isotype controls, were also able to significantly decrease the parasite load in macrophages cultured without theaddition of KMP-11, demonstrating that KMP-11-induced exacerbation of the infection is not dependent on the additionof 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, implicatingit as a virulence factor in L. amazonensis. The stimulation of IL-10 production and arginase activity andthe inhibition of NO synthesis are likely involved in this effect.