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Published on: March 16, 2018
Kinetoplastid membrane protein-11 exacerbates infection with Leishmania amazonensis in murine macrophages
Daniel Ignacchiti Lacerda1, Léa Cysne-Finkelstein, Marise Pinheiro Nunes
1Laboratório de Imunoparasitologia, Instituto Oswaldo Cruz, Rio de Janeiro, RJ, Brasil.
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.
Insights
Kinetoplastid membrane protein-11 (KMP-11) from Leishmania amazonensis worsens macrophage infection by increasing interleukin-10 and arginase while decreasing nitric oxide. This protein is a key virulence factor in Leishmania infection.
Area of Science:
- Parasitology
- Immunology
- Molecular Biology
Background:
- Kinetoplastid membrane protein-11 (KMP-11) expression is upregulated during Leishmania amazonensis meta-cyclogenesis and is higher in amastigotes.
- Higher KMP-11 levels in amastigotes suggest a role in mammalian host infection.
Purpose of the Study:
- To investigate the role of KMP-11 in Leishmania amazonensis infection of mammalian macrophages.
- To determine if KMP-11 acts as a virulence factor by modulating host immune responses.
Main Methods:
- Addition of KMP-11 to peritoneal macrophages from BALB/c mice infected with L. amazonensis.
- Measurement of interleukin-10 (IL-10) and nitric oxide (NO) production.
- Assessment of arginase activity and intracellular amastigote loads.
- Use of anti-KMP-11 and anti-IL-10 neutralizing antibodies.
Main Results:
- KMP-11 exacerbated L. amazonensis infection by increasing IL-10 secretion and arginase activity, while reducing NO production.
- Strong positive correlations were observed between KMP-11 doses, IL-10 levels, and intracellular amastigote loads.
- Neutralizing antibodies against KMP-11 or IL-10 significantly reduced parasite load, indicating KMP-11's intrinsic role.
Conclusions:
- KMP-11 is demonstrated as a virulence factor in Leishmania amazonensis infection.
- KMP-11 exacerbates macrophage infection by stimulating IL-10 and arginase activity and inhibiting NO synthesis.
- The parasite's naturally expressed KMP-11 promotes infection independently of exogenous addition.
