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

Detalhes bibliográficos
Autor(a) principal: Lacerda,Daniel Ignacchiti
Data de Publicação: 2012
Outros Autores: Cysne-Finkelstein,Léa, Nunes,Marise Pinheiro, De-Luca,Paula Mello, Genestra,Marcelo da Silva, Leon,Leonor Laura Pinto, Berrêdo-Pinho,Marcia, Mendonça-Lima,Leila, Matos,Denise Cristina de Souza, Medeiros,Marco Alberto, Mendonça,Sergio Coutinho Furtado de
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Memórias do Instituto Oswaldo Cruz
Texto Completo: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0074-02762012000200014
Resumo: 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.
id FIOCRUZ-4_f4adfba48c3e99d054efcdf1f264d171
oai_identifier_str oai:scielo:S0074-02762012000200014
network_acronym_str FIOCRUZ-4
network_name_str Memórias do Instituto Oswaldo Cruz
spelling Kinetoplastid membrane protein-11 exacerbates infection with Leishmania amazonensis in murine macrophageskinetoplastid membrane protein-11Leishmania amazonensismacrophagesinterleukin-10nitric oxidearginaseIn 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.Instituto Oswaldo Cruz, Ministério da Saúde2012-03-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersiontext/htmlhttp://www.scielo.br/scielo.php?script=sci_arttext&pid=S0074-02762012000200014Memórias do Instituto Oswaldo Cruz v.107 n.2 2012reponame:Memórias do Instituto Oswaldo Cruzinstname:Fundação Oswaldo Cruzinstacron:FIOCRUZ10.1590/S0074-02762012000200014info:eu-repo/semantics/openAccessLacerda,Daniel IgnacchitiCysne-Finkelstein,LéaNunes,Marise PinheiroDe-Luca,Paula MelloGenestra,Marcelo da SilvaLeon,Leonor Laura PintoBerrêdo-Pinho,MarciaMendonça-Lima,LeilaMatos,Denise Cristina de SouzaMedeiros,Marco AlbertoMendonça,Sergio Coutinho Furtado deeng2020-04-25T17:51:09Zhttp://www.scielo.br/oai/scielo-oai.php0074-02761678-8060opendoar:null2020-04-26 02:18:13.359Memórias do Instituto Oswaldo Cruz - Fundação Oswaldo Cruztrue
dc.title.none.fl_str_mv Kinetoplastid membrane protein-11 exacerbates infection with Leishmania amazonensis in murine macrophages
title Kinetoplastid membrane protein-11 exacerbates infection with Leishmania amazonensis in murine macrophages
spellingShingle Kinetoplastid membrane protein-11 exacerbates infection with Leishmania amazonensis in murine macrophages
Lacerda,Daniel Ignacchiti
kinetoplastid membrane protein-11
Leishmania amazonensis
macrophages
interleukin-10
nitric oxide
arginase
title_short Kinetoplastid membrane protein-11 exacerbates infection with Leishmania amazonensis in murine macrophages
title_full Kinetoplastid membrane protein-11 exacerbates infection with Leishmania amazonensis in murine macrophages
title_fullStr Kinetoplastid membrane protein-11 exacerbates infection with Leishmania amazonensis in murine macrophages
title_full_unstemmed Kinetoplastid membrane protein-11 exacerbates infection with Leishmania amazonensis in murine macrophages
title_sort Kinetoplastid membrane protein-11 exacerbates infection with Leishmania amazonensis in murine macrophages
author Lacerda,Daniel Ignacchiti
author_facet Lacerda,Daniel Ignacchiti
Cysne-Finkelstein,Léa
Nunes,Marise Pinheiro
De-Luca,Paula Mello
Genestra,Marcelo da Silva
Leon,Leonor Laura Pinto
Berrêdo-Pinho,Marcia
Mendonça-Lima,Leila
Matos,Denise Cristina de Souza
Medeiros,Marco Alberto
Mendonça,Sergio Coutinho Furtado de
author_role author
author2 Cysne-Finkelstein,Léa
Nunes,Marise Pinheiro
De-Luca,Paula Mello
Genestra,Marcelo da Silva
Leon,Leonor Laura Pinto
Berrêdo-Pinho,Marcia
Mendonça-Lima,Leila
Matos,Denise Cristina de Souza
Medeiros,Marco Alberto
Mendonça,Sergio Coutinho Furtado de
author2_role author
author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Lacerda,Daniel Ignacchiti
Cysne-Finkelstein,Léa
Nunes,Marise Pinheiro
De-Luca,Paula Mello
Genestra,Marcelo da Silva
Leon,Leonor Laura Pinto
Berrêdo-Pinho,Marcia
Mendonça-Lima,Leila
Matos,Denise Cristina de Souza
Medeiros,Marco Alberto
Mendonça,Sergio Coutinho Furtado de
dc.subject.por.fl_str_mv kinetoplastid membrane protein-11
Leishmania amazonensis
macrophages
interleukin-10
nitric oxide
arginase
topic kinetoplastid membrane protein-11
Leishmania amazonensis
macrophages
interleukin-10
nitric oxide
arginase
dc.description.none.fl_txt_mv 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.
description 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.
publishDate 2012
dc.date.none.fl_str_mv 2012-03-01
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0074-02762012000200014
url http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0074-02762012000200014
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 10.1590/S0074-02762012000200014
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv text/html
dc.publisher.none.fl_str_mv Instituto Oswaldo Cruz, Ministério da Saúde
publisher.none.fl_str_mv Instituto Oswaldo Cruz, Ministério da Saúde
dc.source.none.fl_str_mv Memórias do Instituto Oswaldo Cruz v.107 n.2 2012
reponame:Memórias do Instituto Oswaldo Cruz
instname:Fundação Oswaldo Cruz
instacron:FIOCRUZ
reponame_str Memórias do Instituto Oswaldo Cruz
collection Memórias do Instituto Oswaldo Cruz
instname_str Fundação Oswaldo Cruz
instacron_str FIOCRUZ
institution FIOCRUZ
repository.name.fl_str_mv Memórias do Instituto Oswaldo Cruz - Fundação Oswaldo Cruz
repository.mail.fl_str_mv
_version_ 1669937711096528896