Kinetoplastid membrane protein-11 exacerbates infection with Leishmania amazonensis in murine macrophages
Autor(a) principal: | |
---|---|
Data de Publicação: | 2012 |
Outros Autores: | , , , , , , , , , |
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 |