Type I IFN inhibits alternative macrophage activation during mycobacterium tuberculosis infection and leads to enhanced protection in the absence of IFN-gamma signaling
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2016 |
| 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/1822/44807 |
Resumo: | Supplementary material: http://www.jimmunol.org/content/suppl/2016/11/12/jimmunol.1600584.DCSupplemental |
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Type I IFN inhibits alternative macrophage activation during mycobacterium tuberculosis infection and leads to enhanced protection in the absence of IFN-gamma signalingCiências Médicas::Ciências da SaúdeScience & TechnologySupplementary material: http://www.jimmunol.org/content/suppl/2016/11/12/jimmunol.1600584.DCSupplementalTuberculosis causes ∼1.5 million deaths every year, thus remaining a leading cause of death from infectious diseases in the world. A growing body of evidence demonstrates that type I IFN plays a detrimental role in tuberculosis pathogenesis, likely by interfering with IFN-γ–dependent immunity. In this article, we reveal a novel mechanism by which type I IFN may confer protection against Mycobacterium tuberculosis infection in the absence of IFN-γ signaling. We show that production of type I IFN by M. tuberculosis–infected macrophages induced NO synthase 2 and inhibited arginase 1 gene expression. In vivo, absence of both type I and type II IFN receptors led to strikingly increased levels of arginase 1 gene expression and protein activity in infected lungs, characteristic of alternatively activated macrophages. This correlated with increased lung bacterial burden and pathology and decreased survival compared with mice deficient in either receptor. Increased expression of other genes associated with alternatively activated macrophages, as well as increased expression of Th2-associated cytokines and decreased TNF expression, were also observed. Thus, in the absence of IFN-γ signaling, type I IFN suppressed the switching of macrophages from a more protective classically activated phenotype to a more permissive alternatively activated phenotype. Together, our data support a model in which suppression of alternative macrophage activation by type I IFN during M. tuberculosis infection, in the absence of IFN-γ signaling, contributes to host protection.This work was supported by the Fundação para a Ciência e Tecnologia, Portugal, cofunded by Programa Operacional Regional do Norte (ON.2 – O Novo Norte), Quadro de Referência Estratégico Nacional, through the Fundo Europeu de Desenvolvimento Regional (PTDC/SAU-MII/101977/2008 and PTDC/BIA-BCM/102776/2008); by the Francis Crick Institute, which receives its core funding from Cancer Research U.K. (FC001126), the U.K. Medical Research Council (FC001126), and the Wellcome Trust (FC001126); by the U.K. Medical Research Council (MR/U117565642/1); and by the European Research Council (294682-TB-PATH). This work was also supported by Research Grant 2015 from the European Society of Clinical Microbiology and Infectious Diseases (to M.S.). L.M.-T. was funded by the Fundação para a Ciência e Tecnologia (SFRH/BPD/77399/2011) and the European Research Council (294682-TB-PATH). The M.S. laboratory was financed by Fundo Europeu de Desenvolvimento Regional (FEDER) funds through the COMPETE 2020-Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by Portuguese funds through Fundação para a Ciência e Tecnologia, Portugal, in the framework of the Institute for Research and Innovation in Health Sciences project (POCI-01-0145-FEDER-007274). M.S. is a Fundação para a Ciência e Tecnologia Associate Investigator. E.T. is a Fundação para a Ciência e Tecnologia Auxiliary Investigator.American Association of ImmunologistsUniversidade do MinhoMoreira-Teixeira, LúciaSousa, Jeremy Nicolas CarvalhoMcNab, Finlay W.Torrado, EgídioCardoso, FilipaMachado, HenriqueCastro, FláviaCardoso,VâniaGaifem, JoanaWu, XuemeiAppelberg, RuiCastro, António G.O’Garra, AnneSaraiva, Margarida20162016-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/44807engMoreira-Teixeira, L., Sousa, J., McNab, F. W., Torrado, E., Cardoso, F., Machado, H., . . . Saraiva, M. (2016). Type i IFN inhibits alternative macrophage activation during mycobacterium tuberculosis infection and leads to enhanced protection in the absence of IFN-γ signaling. [Article]. Journal of Immunology, 197(12), 4714-4726. doi: 10.4049/jimmunol.16005840022-17671550-660610.4049/jimmunol.160058427849167www.jimmunol.org/cgi/doi/10.4049/jimmunol.1600584info: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:RCAAP2023-07-21T12:48:28Zoai:repositorium.sdum.uminho.pt:1822/44807Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:46:44.378365Repositório 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 |
Type I IFN inhibits alternative macrophage activation during mycobacterium tuberculosis infection and leads to enhanced protection in the absence of IFN-gamma signaling |
| title |
Type I IFN inhibits alternative macrophage activation during mycobacterium tuberculosis infection and leads to enhanced protection in the absence of IFN-gamma signaling |
| spellingShingle |
Type I IFN inhibits alternative macrophage activation during mycobacterium tuberculosis infection and leads to enhanced protection in the absence of IFN-gamma signaling Moreira-Teixeira, Lúcia Ciências Médicas::Ciências da Saúde Science & Technology |
| title_short |
Type I IFN inhibits alternative macrophage activation during mycobacterium tuberculosis infection and leads to enhanced protection in the absence of IFN-gamma signaling |
| title_full |
Type I IFN inhibits alternative macrophage activation during mycobacterium tuberculosis infection and leads to enhanced protection in the absence of IFN-gamma signaling |
| title_fullStr |
Type I IFN inhibits alternative macrophage activation during mycobacterium tuberculosis infection and leads to enhanced protection in the absence of IFN-gamma signaling |
| title_full_unstemmed |
Type I IFN inhibits alternative macrophage activation during mycobacterium tuberculosis infection and leads to enhanced protection in the absence of IFN-gamma signaling |
| title_sort |
Type I IFN inhibits alternative macrophage activation during mycobacterium tuberculosis infection and leads to enhanced protection in the absence of IFN-gamma signaling |
| author |
Moreira-Teixeira, Lúcia |
| author_facet |
Moreira-Teixeira, Lúcia Sousa, Jeremy Nicolas Carvalho McNab, Finlay W. Torrado, Egídio Cardoso, Filipa Machado, Henrique Castro, Flávia Cardoso,Vânia Gaifem, Joana Wu, Xuemei Appelberg, Rui Castro, António G. O’Garra, Anne Saraiva, Margarida |
| author_role |
author |
| author2 |
Sousa, Jeremy Nicolas Carvalho McNab, Finlay W. Torrado, Egídio Cardoso, Filipa Machado, Henrique Castro, Flávia Cardoso,Vânia Gaifem, Joana Wu, Xuemei Appelberg, Rui Castro, António G. O’Garra, Anne Saraiva, Margarida |
| author2_role |
author author 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 |
Moreira-Teixeira, Lúcia Sousa, Jeremy Nicolas Carvalho McNab, Finlay W. Torrado, Egídio Cardoso, Filipa Machado, Henrique Castro, Flávia Cardoso,Vânia Gaifem, Joana Wu, Xuemei Appelberg, Rui Castro, António G. O’Garra, Anne Saraiva, Margarida |
| dc.subject.por.fl_str_mv |
Ciências Médicas::Ciências da Saúde Science & Technology |
| topic |
Ciências Médicas::Ciências da Saúde Science & Technology |
| description |
Supplementary material: http://www.jimmunol.org/content/suppl/2016/11/12/jimmunol.1600584.DCSupplemental |
| publishDate |
2016 |
| dc.date.none.fl_str_mv |
2016 2016-01-01T00:00:00Z |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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publishedVersion |
| dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/1822/44807 |
| url |
http://hdl.handle.net/1822/44807 |
| dc.language.iso.fl_str_mv |
eng |
| language |
eng |
| dc.relation.none.fl_str_mv |
Moreira-Teixeira, L., Sousa, J., McNab, F. W., Torrado, E., Cardoso, F., Machado, H., . . . Saraiva, M. (2016). Type i IFN inhibits alternative macrophage activation during mycobacterium tuberculosis infection and leads to enhanced protection in the absence of IFN-γ signaling. [Article]. Journal of Immunology, 197(12), 4714-4726. doi: 10.4049/jimmunol.1600584 0022-1767 1550-6606 10.4049/jimmunol.1600584 27849167 www.jimmunol.org/cgi/doi/10.4049/jimmunol.1600584 |
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info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
| dc.publisher.none.fl_str_mv |
American Association of Immunologists |
| publisher.none.fl_str_mv |
American Association of Immunologists |
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