Leishmania infantum exoproducts inhibit human invariant NKT cell expansion and activation
Autor(a) principal: | |
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Data de Publicação: | 2017 |
Outros Autores: | , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | https://repositorio-aberto.up.pt/handle/10216/118198 |
Resumo: | Leishmania infantum is one of the major parasite species associated with visceral leishmaniasis, a severe form of the disease that can become lethal if untreated. This obligate intracellular parasite has developed diverse strategies to escape the host immune response, such as exoproducts (Exo) carrying a wide range of molecules, including parasite virulence factors, which are potentially implicated in early stages of infection. Herein, we report that L. infantum Exo and its two fractions composed of extracellular vesicles (EVs) and vesicle-depleted-exoproducts (VDEs) inhibit human peripheral blood invariant natural killer T (iNKT) cell expansion in response to their specific ligand, the glycolipid a-GalactosylCeramide (a-GalCer), as well as their capacity to promptly produce IL-4 and IFN¿. Using plate-bound CD1d and a-GalCer, we found that Exo, EV, and VDE fractions reduced iNKT cell activation in a dose-dependent manner, suggesting that they prevented a-GalCer presentation by CD1d molecules. This direct effect on CD1d was confirmed by the observation that CD1d:a-GalCer complex formation was impaired in the presence of Exo, EV, and VDE fractions. Furthermore, lipid extracts from the three compounds mimicked the inhibition of iNKT cell activation. These lipid components of L. infantum exoproducts, including EV and VDE fractions, might compete for CD1-binding sites, thus blocking iNKT cell activation. Overall, our results provide evidence for a novel strategy through which L. infantum can evade immune responses of mammalian host cells by preventing iNKT lymphocytes from recognizing glycolipids in a TCR-dependent manner. |
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Leishmania infantum exoproducts inhibit human invariant NKT cell expansion and activationLeishmaniaNKT cellsexoproductparasite escapeperipheral blood mononuclear cellLeishmania infantum is one of the major parasite species associated with visceral leishmaniasis, a severe form of the disease that can become lethal if untreated. This obligate intracellular parasite has developed diverse strategies to escape the host immune response, such as exoproducts (Exo) carrying a wide range of molecules, including parasite virulence factors, which are potentially implicated in early stages of infection. Herein, we report that L. infantum Exo and its two fractions composed of extracellular vesicles (EVs) and vesicle-depleted-exoproducts (VDEs) inhibit human peripheral blood invariant natural killer T (iNKT) cell expansion in response to their specific ligand, the glycolipid a-GalactosylCeramide (a-GalCer), as well as their capacity to promptly produce IL-4 and IFN¿. Using plate-bound CD1d and a-GalCer, we found that Exo, EV, and VDE fractions reduced iNKT cell activation in a dose-dependent manner, suggesting that they prevented a-GalCer presentation by CD1d molecules. This direct effect on CD1d was confirmed by the observation that CD1d:a-GalCer complex formation was impaired in the presence of Exo, EV, and VDE fractions. Furthermore, lipid extracts from the three compounds mimicked the inhibition of iNKT cell activation. These lipid components of L. infantum exoproducts, including EV and VDE fractions, might compete for CD1-binding sites, thus blocking iNKT cell activation. Overall, our results provide evidence for a novel strategy through which L. infantum can evade immune responses of mammalian host cells by preventing iNKT lymphocytes from recognizing glycolipids in a TCR-dependent manner.Frontiers Media20172017-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttps://repositorio-aberto.up.pt/handle/10216/118198eng1664-322410.3389/fimmu.2017.00710Belo, RSantarém, NPereira, CPérez-Cabezas, BMacedo, FLeite-de-Moraes, MCordeiro-da-Silva, Ainfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-29T14:49:12Zoai:repositorio-aberto.up.pt:10216/118198Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T00:09:14.627584Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Leishmania infantum exoproducts inhibit human invariant NKT cell expansion and activation |
title |
Leishmania infantum exoproducts inhibit human invariant NKT cell expansion and activation |
spellingShingle |
Leishmania infantum exoproducts inhibit human invariant NKT cell expansion and activation Belo, R Leishmania NKT cells exoproduct parasite escape peripheral blood mononuclear cell |
title_short |
Leishmania infantum exoproducts inhibit human invariant NKT cell expansion and activation |
title_full |
Leishmania infantum exoproducts inhibit human invariant NKT cell expansion and activation |
title_fullStr |
Leishmania infantum exoproducts inhibit human invariant NKT cell expansion and activation |
title_full_unstemmed |
Leishmania infantum exoproducts inhibit human invariant NKT cell expansion and activation |
title_sort |
Leishmania infantum exoproducts inhibit human invariant NKT cell expansion and activation |
author |
Belo, R |
author_facet |
Belo, R Santarém, N Pereira, C Pérez-Cabezas, B Macedo, F Leite-de-Moraes, M Cordeiro-da-Silva, A |
author_role |
author |
author2 |
Santarém, N Pereira, C Pérez-Cabezas, B Macedo, F Leite-de-Moraes, M Cordeiro-da-Silva, A |
author2_role |
author author author author author author |
dc.contributor.author.fl_str_mv |
Belo, R Santarém, N Pereira, C Pérez-Cabezas, B Macedo, F Leite-de-Moraes, M Cordeiro-da-Silva, A |
dc.subject.por.fl_str_mv |
Leishmania NKT cells exoproduct parasite escape peripheral blood mononuclear cell |
topic |
Leishmania NKT cells exoproduct parasite escape peripheral blood mononuclear cell |
description |
Leishmania infantum is one of the major parasite species associated with visceral leishmaniasis, a severe form of the disease that can become lethal if untreated. This obligate intracellular parasite has developed diverse strategies to escape the host immune response, such as exoproducts (Exo) carrying a wide range of molecules, including parasite virulence factors, which are potentially implicated in early stages of infection. Herein, we report that L. infantum Exo and its two fractions composed of extracellular vesicles (EVs) and vesicle-depleted-exoproducts (VDEs) inhibit human peripheral blood invariant natural killer T (iNKT) cell expansion in response to their specific ligand, the glycolipid a-GalactosylCeramide (a-GalCer), as well as their capacity to promptly produce IL-4 and IFN¿. Using plate-bound CD1d and a-GalCer, we found that Exo, EV, and VDE fractions reduced iNKT cell activation in a dose-dependent manner, suggesting that they prevented a-GalCer presentation by CD1d molecules. This direct effect on CD1d was confirmed by the observation that CD1d:a-GalCer complex formation was impaired in the presence of Exo, EV, and VDE fractions. Furthermore, lipid extracts from the three compounds mimicked the inhibition of iNKT cell activation. These lipid components of L. infantum exoproducts, including EV and VDE fractions, might compete for CD1-binding sites, thus blocking iNKT cell activation. Overall, our results provide evidence for a novel strategy through which L. infantum can evade immune responses of mammalian host cells by preventing iNKT lymphocytes from recognizing glycolipids in a TCR-dependent manner. |
publishDate |
2017 |
dc.date.none.fl_str_mv |
2017 2017-01-01T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
https://repositorio-aberto.up.pt/handle/10216/118198 |
url |
https://repositorio-aberto.up.pt/handle/10216/118198 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
1664-3224 10.3389/fimmu.2017.00710 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Frontiers Media |
publisher.none.fl_str_mv |
Frontiers Media |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
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1799136017604673536 |