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

Abstract

In Leishmania amazonensis, kinetoplastid membrane protein-11 (KMP-11) expression increases during meta-cyclogenesis 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.

• Authors: Daniel Ignacchiti Lacerda, Léa Cysne-Finkelstein, Marise Pinheiro Nunes, Paula Mello De-Luca, Marcelo da Silva Genestra, Leonor Laura Pinto Leon, Marcia Berrêdo-Pinho, Leila Mendonça-Lima, Denise Cristina de Souza Matos, Marco Alberto Medeiros, Sergio Coutinho Furtado de Mendonça
• Journal: Memorias do Instituto Oswaldo Cruz (Mem Inst Oswaldo Cruz) Vol. 107 Issue 2 Pg. 238-45 (Mar 2012) ISSN: 1678-8060 [Electronic] Brazil
• PMID: 22415264 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Membrane Proteins
• Protozoan Proteins
• kinetoplastid membrane protein-11, Leishmania amazonensis
• Interleukin-10
• Nitric Oxide
• Arginase

Topics

• Animals
• Arginase (metabolism)
• Cells, Cultured
• Female
• Interleukin-10 (immunology, metabolism)
• Leishmania mexicana (drug effects, immunology)
• Macrophages, Peritoneal (enzymology, immunology, parasitology)
• Membrane Proteins (pharmacology)
• Mice
• Mice, Inbred BALB C
• Nitric Oxide (biosynthesis)
• Protozoan Proteins (pharmacology)