title: 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.affiliation: Laboratório de Imunoparasitologia, Instituto Oswaldo Cruz, Rio de Janeiro, RJ, Brasil.
authors.forename: Daniel Ignacchiti
authors.initials: DI
authors.lastname: Lacerda
authors.forename: Léa
authors.initials: L
authors.lastname: Cysne-Finkelstein
authors.forename: Marise Pinheiro
authors.initials: MP
authors.lastname: Nunes
authors.forename: Paula Mello
authors.initials: PM
authors.lastname: De-Luca
authors.forename: Marcelo da Silva
authors.initials: Mda S
authors.lastname: Genestra
authors.forename: Leonor Laura Pinto
authors.initials: LL
authors.lastname: Leon
authors.forename: Marcia
authors.initials: M
authors.lastname: Berrêdo-Pinho
authors.forename: Leila
authors.initials: L
authors.lastname: Mendonça-Lima
authors.forename: Denise Cristina de Souza
authors.initials: DC
authors.lastname: Matos
authors.forename: Marco Alberto
authors.initials: MA
authors.lastname: Medeiros
authors.forename: Sergio Coutinho Furtado de
authors.initials: SC
authors.lastname: Mendonça
mesh_terms: D000818:Animals; D001119:Arginase / Q000378:metabolism*; D002478:Cells, Cultured; D005260:Female; D016753:Interleukin-10 / Q000276:immunology* / Q000378:metabolism; D007894:Leishmania mexicana / Q000187:drug effects* / Q000276:immunology; D017737:Macrophages, Peritoneal / Q000201:enzymology / Q000276:immunology / Q000469:parasitology*; D008565:Membrane Proteins / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000096:biosynthesis*; D015800:Protozoan Proteins / Q000494:pharmacology*
chemical_list: D008565:Membrane Proteins; D015800:Protozoan Proteins; C551389:kinetoplastid membrane protein-11, Leishmania amazonensis; D016753:Interleukin-10; D009569:Nitric Oxide; D001119:Arginase