The Warburg effect in mycobacterial granulomas is dependent on the recruitment and activation of macrophages by interferon-γ
Autor(a) principal: | |
---|---|
Data de Publicação: | 2015 |
Outros Autores: | , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/1822/40065 |
Resumo: | Granulomas are the hallmark of mycobacterial disease. Here, we demonstrate that both the cell recruitment and the increased glucose consumption in granulomatous infiltrates during Mycobacterium avium infection are highly dependent on interferon-y (IFN-y). Mycobacterium avium-infected mice lacking IFN-y signalling failed to developed significant inflammatory infiltrations and lacked the characteristic uptake of the glucose analogue fluorine-18-fluorodeoxyglucose (FDG). To assess the role of macrophages in glucose uptake we infected mice with a selective impairment of IFN-y signalling in the macrophage lineage (MIIG mice). Although only a partial reduction of the granulomatous areas was observed in infected MIIG mice, the insensitivity of macrophages to IFN-y reduced the accumulation of FDG. In vivo, ex vivo and in vitro assays showed that macrophage activated by IFN-y displayed increased rates of glucose uptake and in vitro studies showed also that they had increased lactate production and increased expression of key glycolytic enzymes. Overall, our results show that the activation of macrophages by IFN-y is responsible for the Warburg effect observed in organs infected with M. avium. |
id |
RCAP_12347bee84a4722c0b178c9193a59b10 |
---|---|
oai_identifier_str |
oai:repositorium.sdum.uminho.pt:1822/40065 |
network_acronym_str |
RCAP |
network_name_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository_id_str |
7160 |
spelling |
The Warburg effect in mycobacterial granulomas is dependent on the recruitment and activation of macrophages by interferon-γGlycolysisInfectionInterferon-γMacrophagesMycobacteriainterferon-gammaInterferon-?Ciências Médicas::Ciências da SaúdeScience & TechnologyGranulomas are the hallmark of mycobacterial disease. Here, we demonstrate that both the cell recruitment and the increased glucose consumption in granulomatous infiltrates during Mycobacterium avium infection are highly dependent on interferon-y (IFN-y). Mycobacterium avium-infected mice lacking IFN-y signalling failed to developed significant inflammatory infiltrations and lacked the characteristic uptake of the glucose analogue fluorine-18-fluorodeoxyglucose (FDG). To assess the role of macrophages in glucose uptake we infected mice with a selective impairment of IFN-y signalling in the macrophage lineage (MIIG mice). Although only a partial reduction of the granulomatous areas was observed in infected MIIG mice, the insensitivity of macrophages to IFN-y reduced the accumulation of FDG. In vivo, ex vivo and in vitro assays showed that macrophage activated by IFN-y displayed increased rates of glucose uptake and in vitro studies showed also that they had increased lactate production and increased expression of key glycolytic enzymes. Overall, our results show that the activation of macrophages by IFN-y is responsible for the Warburg effect observed in organs infected with M. avium.Funded by project ‘NORTE-07-0124-FEDER-000002-Host-Pathogen Interactions’ co-funded by Programa Operacional Regional do Norte (ON.2—O Novo Norte), under the Quadro de Referência Estratégico Nacional (QREN), through the Fundo Europeu de Desenvolvimento Regional (FEDER) and by Fundação para a Ciência e Tecnologia.WileyUniversidade do MinhoAppelberg, RuiMoreira, DianaSilva, Palmira Conceição Araújo BarreiraBorges, MargaridaSilva, LetíciaDinis-Oliveira, Ricardo JorgeResende, MarianaNeves, Margarida CorreiaJordan, Michael B.Ferreira, Nuno C.Abrunhosa, Antero J.Silvestre, Ricardo Jorge Leal2015-082015-08-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/40065engAppelberg, R., Moreira, D., Barreira-Silva, P., Borges, M., Silva, L., Dinis-Oliveira, R. J., . . . Silvestre, R. (2015). The Warburg effect in mycobacterial granulomas is dependent on the recruitment and activation of macrophages by interferon-γ. Immunology. doi: 10.1111/imm.124640019-280510.1111/imm.1246425807843http://onlinelibrary.wiley.com/doi/10.1111/imm.12464/fullinfo: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:RCAAP2023-07-21T12:23:16Zoai:repositorium.sdum.uminho.pt:1822/40065Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:16:57.612644Repositório 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 |
The Warburg effect in mycobacterial granulomas is dependent on the recruitment and activation of macrophages by interferon-γ |
title |
The Warburg effect in mycobacterial granulomas is dependent on the recruitment and activation of macrophages by interferon-γ |
spellingShingle |
The Warburg effect in mycobacterial granulomas is dependent on the recruitment and activation of macrophages by interferon-γ Appelberg, Rui Glycolysis Infection Interferon-γ Macrophages Mycobacteria interferon-gamma Interferon-? Ciências Médicas::Ciências da Saúde Science & Technology |
title_short |
The Warburg effect in mycobacterial granulomas is dependent on the recruitment and activation of macrophages by interferon-γ |
title_full |
The Warburg effect in mycobacterial granulomas is dependent on the recruitment and activation of macrophages by interferon-γ |
title_fullStr |
The Warburg effect in mycobacterial granulomas is dependent on the recruitment and activation of macrophages by interferon-γ |
title_full_unstemmed |
The Warburg effect in mycobacterial granulomas is dependent on the recruitment and activation of macrophages by interferon-γ |
title_sort |
The Warburg effect in mycobacterial granulomas is dependent on the recruitment and activation of macrophages by interferon-γ |
author |
Appelberg, Rui |
author_facet |
Appelberg, Rui Moreira, Diana Silva, Palmira Conceição Araújo Barreira Borges, Margarida Silva, Letícia Dinis-Oliveira, Ricardo Jorge Resende, Mariana Neves, Margarida Correia Jordan, Michael B. Ferreira, Nuno C. Abrunhosa, Antero J. Silvestre, Ricardo Jorge Leal |
author_role |
author |
author2 |
Moreira, Diana Silva, Palmira Conceição Araújo Barreira Borges, Margarida Silva, Letícia Dinis-Oliveira, Ricardo Jorge Resende, Mariana Neves, Margarida Correia Jordan, Michael B. Ferreira, Nuno C. Abrunhosa, Antero J. Silvestre, Ricardo Jorge Leal |
author2_role |
author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade do Minho |
dc.contributor.author.fl_str_mv |
Appelberg, Rui Moreira, Diana Silva, Palmira Conceição Araújo Barreira Borges, Margarida Silva, Letícia Dinis-Oliveira, Ricardo Jorge Resende, Mariana Neves, Margarida Correia Jordan, Michael B. Ferreira, Nuno C. Abrunhosa, Antero J. Silvestre, Ricardo Jorge Leal |
dc.subject.por.fl_str_mv |
Glycolysis Infection Interferon-γ Macrophages Mycobacteria interferon-gamma Interferon-? Ciências Médicas::Ciências da Saúde Science & Technology |
topic |
Glycolysis Infection Interferon-γ Macrophages Mycobacteria interferon-gamma Interferon-? Ciências Médicas::Ciências da Saúde Science & Technology |
description |
Granulomas are the hallmark of mycobacterial disease. Here, we demonstrate that both the cell recruitment and the increased glucose consumption in granulomatous infiltrates during Mycobacterium avium infection are highly dependent on interferon-y (IFN-y). Mycobacterium avium-infected mice lacking IFN-y signalling failed to developed significant inflammatory infiltrations and lacked the characteristic uptake of the glucose analogue fluorine-18-fluorodeoxyglucose (FDG). To assess the role of macrophages in glucose uptake we infected mice with a selective impairment of IFN-y signalling in the macrophage lineage (MIIG mice). Although only a partial reduction of the granulomatous areas was observed in infected MIIG mice, the insensitivity of macrophages to IFN-y reduced the accumulation of FDG. In vivo, ex vivo and in vitro assays showed that macrophage activated by IFN-y displayed increased rates of glucose uptake and in vitro studies showed also that they had increased lactate production and increased expression of key glycolytic enzymes. Overall, our results show that the activation of macrophages by IFN-y is responsible for the Warburg effect observed in organs infected with M. avium. |
publishDate |
2015 |
dc.date.none.fl_str_mv |
2015-08 2015-08-01T00:00:00Z |
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 |
http://hdl.handle.net/1822/40065 |
url |
http://hdl.handle.net/1822/40065 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Appelberg, R., Moreira, D., Barreira-Silva, P., Borges, M., Silva, L., Dinis-Oliveira, R. J., . . . Silvestre, R. (2015). The Warburg effect in mycobacterial granulomas is dependent on the recruitment and activation of macrophages by interferon-γ. Immunology. doi: 10.1111/imm.12464 0019-2805 10.1111/imm.12464 25807843 http://onlinelibrary.wiley.com/doi/10.1111/imm.12464/full |
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 |
Wiley |
publisher.none.fl_str_mv |
Wiley |
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 |
|
_version_ |
1799132620578095104 |