Molecular and cellular mechanisms of Mycobacterium avium-induced thymic atrophy
Autor(a) principal: | |
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Data de Publicação: | 2012 |
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/1822/22115 |
Resumo: | Thymic atrophy has been described as a consequence of infection by several pathogens and shown to be induced through diverse mechanisms. Using the mouse model of Mycobacterium avium infection, we show in this study that the production of NO from IFN-γ–activated macrophages plays a major role in mycobacterial infection-induced thymic atrophy. Our results show that disseminated infection with a highly virulent strain of M. avium, but not with a low-virulence strain, led to a progressive thymic atrophy. Thymic involution was prevented in genetically manipulated mice unable to produce IFN-γ or the inducible NO synthase. In addition, mice with a selective impairment of IFN-γ signaling in macrophages were similarly protected from infection-induced thymic atrophy. A slight increase in the concentration of corticosterone was found in mice infected with the highly virulent strain, and thymocytes presented an increased susceptibility to dexamethasone-induced death during disseminated infection. The administration of an antagonist of glucocorticoid receptors partially reverted the infection-induced thymic atrophy. We observed a reduction in all thymocyte populations analyzed, including the earliest thymic precursors, suggesting a defect during thymic colonization by T cell precursors and/or during the differentiation of these cells in the bone marrow in addition to local demise of thymic cells. Our data suggest a complex picture underlying thymic atrophy during infection by M. avium with the participation of locally produced NO, endogenous corticosteroid activity, and reduced bone marrow seeding. |
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Molecular and cellular mechanisms of Mycobacterium avium-induced thymic atrophyInfectionMycobacteriaThymus atrophyNitric oxideGamma interferonCorticosteroneScience & TechnologyThymic atrophy has been described as a consequence of infection by several pathogens and shown to be induced through diverse mechanisms. Using the mouse model of Mycobacterium avium infection, we show in this study that the production of NO from IFN-γ–activated macrophages plays a major role in mycobacterial infection-induced thymic atrophy. Our results show that disseminated infection with a highly virulent strain of M. avium, but not with a low-virulence strain, led to a progressive thymic atrophy. Thymic involution was prevented in genetically manipulated mice unable to produce IFN-γ or the inducible NO synthase. In addition, mice with a selective impairment of IFN-γ signaling in macrophages were similarly protected from infection-induced thymic atrophy. A slight increase in the concentration of corticosterone was found in mice infected with the highly virulent strain, and thymocytes presented an increased susceptibility to dexamethasone-induced death during disseminated infection. The administration of an antagonist of glucocorticoid receptors partially reverted the infection-induced thymic atrophy. We observed a reduction in all thymocyte populations analyzed, including the earliest thymic precursors, suggesting a defect during thymic colonization by T cell precursors and/or during the differentiation of these cells in the bone marrow in addition to local demise of thymic cells. Our data suggest a complex picture underlying thymic atrophy during infection by M. avium with the participation of locally produced NO, endogenous corticosteroid activity, and reduced bone marrow seeding.Fundo Europeu de Desenvolvimento Regional - 011142 (reference PTDC/SAU-MII/099102/ 2008Fundação para a Ciência e a Tecnologia (FCT) - PTDC/SAU-MII/101663/2008National Institutes of Health - R01HL091769American Association of ImmunologistsUniversidade do MinhoBorges, MargaridaSilva, Palmira Conceição Araújo BarreiraFlórido, ManuelaJordan, Michael B.Neves, Margarida CorreiaAppelberg, Rui2012-102012-10-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/22115eng0022-176710.4049/jimmunol.120152522922815http://www.jimmunol.org/info: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:RCAAP2023-07-21T12:30:31Zoai:repositorium.sdum.uminho.pt:1822/22115Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:25:42.789232Repositório 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 |
Molecular and cellular mechanisms of Mycobacterium avium-induced thymic atrophy |
title |
Molecular and cellular mechanisms of Mycobacterium avium-induced thymic atrophy |
spellingShingle |
Molecular and cellular mechanisms of Mycobacterium avium-induced thymic atrophy Borges, Margarida Infection Mycobacteria Thymus atrophy Nitric oxide Gamma interferon Corticosterone Science & Technology |
title_short |
Molecular and cellular mechanisms of Mycobacterium avium-induced thymic atrophy |
title_full |
Molecular and cellular mechanisms of Mycobacterium avium-induced thymic atrophy |
title_fullStr |
Molecular and cellular mechanisms of Mycobacterium avium-induced thymic atrophy |
title_full_unstemmed |
Molecular and cellular mechanisms of Mycobacterium avium-induced thymic atrophy |
title_sort |
Molecular and cellular mechanisms of Mycobacterium avium-induced thymic atrophy |
author |
Borges, Margarida |
author_facet |
Borges, Margarida Silva, Palmira Conceição Araújo Barreira Flórido, Manuela Jordan, Michael B. Neves, Margarida Correia Appelberg, Rui |
author_role |
author |
author2 |
Silva, Palmira Conceição Araújo Barreira Flórido, Manuela Jordan, Michael B. Neves, Margarida Correia Appelberg, Rui |
author2_role |
author author author author author |
dc.contributor.none.fl_str_mv |
Universidade do Minho |
dc.contributor.author.fl_str_mv |
Borges, Margarida Silva, Palmira Conceição Araújo Barreira Flórido, Manuela Jordan, Michael B. Neves, Margarida Correia Appelberg, Rui |
dc.subject.por.fl_str_mv |
Infection Mycobacteria Thymus atrophy Nitric oxide Gamma interferon Corticosterone Science & Technology |
topic |
Infection Mycobacteria Thymus atrophy Nitric oxide Gamma interferon Corticosterone Science & Technology |
description |
Thymic atrophy has been described as a consequence of infection by several pathogens and shown to be induced through diverse mechanisms. Using the mouse model of Mycobacterium avium infection, we show in this study that the production of NO from IFN-γ–activated macrophages plays a major role in mycobacterial infection-induced thymic atrophy. Our results show that disseminated infection with a highly virulent strain of M. avium, but not with a low-virulence strain, led to a progressive thymic atrophy. Thymic involution was prevented in genetically manipulated mice unable to produce IFN-γ or the inducible NO synthase. In addition, mice with a selective impairment of IFN-γ signaling in macrophages were similarly protected from infection-induced thymic atrophy. A slight increase in the concentration of corticosterone was found in mice infected with the highly virulent strain, and thymocytes presented an increased susceptibility to dexamethasone-induced death during disseminated infection. The administration of an antagonist of glucocorticoid receptors partially reverted the infection-induced thymic atrophy. We observed a reduction in all thymocyte populations analyzed, including the earliest thymic precursors, suggesting a defect during thymic colonization by T cell precursors and/or during the differentiation of these cells in the bone marrow in addition to local demise of thymic cells. Our data suggest a complex picture underlying thymic atrophy during infection by M. avium with the participation of locally produced NO, endogenous corticosteroid activity, and reduced bone marrow seeding. |
publishDate |
2012 |
dc.date.none.fl_str_mv |
2012-10 2012-10-01T00:00:00Z |
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/1822/22115 |
url |
http://hdl.handle.net/1822/22115 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
0022-1767 10.4049/jimmunol.1201525 22922815 http://www.jimmunol.org/ |
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 |
American Association of Immunologists |
publisher.none.fl_str_mv |
American Association of Immunologists |
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 |
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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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1799132742076596224 |