Heme Catabolism by Heme Oxygenase-1 Confers Host Resistance to Mycobacterium Infection
Autor(a) principal: | |
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Data de Publicação: | 2013 |
Outros Autores: | , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | https://hdl.handle.net/10216/69106 |
Resumo: | Heme oxygenases (HO) catalyze the rate-limiting step of heme degradation. The cytoprotective action of the inducible HO-1 isoform, encoded by the Hmox1 gene, is required for host protection against systemic infections. Here we report that upregulation of HO-1 expression in macrophages (M phi) is strictly required for protection against mycobacterial infection in mice. HO-1-deficient (Hmox1(-/-)) mice are more susceptible to intravenous Mycobacterium avium infection, failing to mount a protective granulomatous response and developing higher pathogen loads, than infected wild-type (Hmox1(+/+)) controls. Furthermore, Hmox1(-/-) mice also develop higher pathogen loads and ultimately succumb when challenged with a low-dose aerosol infection with Mycobacterium tuberculosis. The protective effect of HO-1 acts independently of adaptive immunity, as revealed in M. avium-infected Hmox1(-/-) versus Hmox1(+/+) SCID mice lacking mature B and T cells. In the absence of HO-1, heme accumulation acts as a cytotoxic pro-oxidant in infected M phi, an effect mimicked by exogenous heme administration to M. avium-infected wild-type M phi in vitro or to mice in vivo. In conclusion, HO-1 prevents the cytotoxic effect of heme in M phi, contributing critically to host resistance to Mycobacterium infection. |
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Heme Catabolism by Heme Oxygenase-1 Confers Host Resistance to Mycobacterium InfectionInfecções, Medicina básicaInfections, Basic medicineHeme oxygenases (HO) catalyze the rate-limiting step of heme degradation. The cytoprotective action of the inducible HO-1 isoform, encoded by the Hmox1 gene, is required for host protection against systemic infections. Here we report that upregulation of HO-1 expression in macrophages (M phi) is strictly required for protection against mycobacterial infection in mice. HO-1-deficient (Hmox1(-/-)) mice are more susceptible to intravenous Mycobacterium avium infection, failing to mount a protective granulomatous response and developing higher pathogen loads, than infected wild-type (Hmox1(+/+)) controls. Furthermore, Hmox1(-/-) mice also develop higher pathogen loads and ultimately succumb when challenged with a low-dose aerosol infection with Mycobacterium tuberculosis. The protective effect of HO-1 acts independently of adaptive immunity, as revealed in M. avium-infected Hmox1(-/-) versus Hmox1(+/+) SCID mice lacking mature B and T cells. In the absence of HO-1, heme accumulation acts as a cytotoxic pro-oxidant in infected M phi, an effect mimicked by exogenous heme administration to M. avium-infected wild-type M phi in vitro or to mice in vivo. In conclusion, HO-1 prevents the cytotoxic effect of heme in M phi, contributing critically to host resistance to Mycobacterium infection.20132013-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10216/69106eng0019-956710.1128/iai.00251-13Sandro Silva GomesRui AppelbergRasmus LarsenMiguel Parreira SoaresMaria Salome Gomesinfo: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:RCAAP2023-11-29T12:32:54Zoai:repositorio-aberto.up.pt:10216/69106Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T23:22:21.547851Repositório 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 |
Heme Catabolism by Heme Oxygenase-1 Confers Host Resistance to Mycobacterium Infection |
title |
Heme Catabolism by Heme Oxygenase-1 Confers Host Resistance to Mycobacterium Infection |
spellingShingle |
Heme Catabolism by Heme Oxygenase-1 Confers Host Resistance to Mycobacterium Infection Sandro Silva Gomes Infecções, Medicina básica Infections, Basic medicine |
title_short |
Heme Catabolism by Heme Oxygenase-1 Confers Host Resistance to Mycobacterium Infection |
title_full |
Heme Catabolism by Heme Oxygenase-1 Confers Host Resistance to Mycobacterium Infection |
title_fullStr |
Heme Catabolism by Heme Oxygenase-1 Confers Host Resistance to Mycobacterium Infection |
title_full_unstemmed |
Heme Catabolism by Heme Oxygenase-1 Confers Host Resistance to Mycobacterium Infection |
title_sort |
Heme Catabolism by Heme Oxygenase-1 Confers Host Resistance to Mycobacterium Infection |
author |
Sandro Silva Gomes |
author_facet |
Sandro Silva Gomes Rui Appelberg Rasmus Larsen Miguel Parreira Soares Maria Salome Gomes |
author_role |
author |
author2 |
Rui Appelberg Rasmus Larsen Miguel Parreira Soares Maria Salome Gomes |
author2_role |
author author author author |
dc.contributor.author.fl_str_mv |
Sandro Silva Gomes Rui Appelberg Rasmus Larsen Miguel Parreira Soares Maria Salome Gomes |
dc.subject.por.fl_str_mv |
Infecções, Medicina básica Infections, Basic medicine |
topic |
Infecções, Medicina básica Infections, Basic medicine |
description |
Heme oxygenases (HO) catalyze the rate-limiting step of heme degradation. The cytoprotective action of the inducible HO-1 isoform, encoded by the Hmox1 gene, is required for host protection against systemic infections. Here we report that upregulation of HO-1 expression in macrophages (M phi) is strictly required for protection against mycobacterial infection in mice. HO-1-deficient (Hmox1(-/-)) mice are more susceptible to intravenous Mycobacterium avium infection, failing to mount a protective granulomatous response and developing higher pathogen loads, than infected wild-type (Hmox1(+/+)) controls. Furthermore, Hmox1(-/-) mice also develop higher pathogen loads and ultimately succumb when challenged with a low-dose aerosol infection with Mycobacterium tuberculosis. The protective effect of HO-1 acts independently of adaptive immunity, as revealed in M. avium-infected Hmox1(-/-) versus Hmox1(+/+) SCID mice lacking mature B and T cells. In the absence of HO-1, heme accumulation acts as a cytotoxic pro-oxidant in infected M phi, an effect mimicked by exogenous heme administration to M. avium-infected wild-type M phi in vitro or to mice in vivo. In conclusion, HO-1 prevents the cytotoxic effect of heme in M phi, contributing critically to host resistance to Mycobacterium infection. |
publishDate |
2013 |
dc.date.none.fl_str_mv |
2013 2013-01-01T00:00:00Z |
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://hdl.handle.net/10216/69106 |
url |
https://hdl.handle.net/10216/69106 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
0019-9567 10.1128/iai.00251-13 |
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.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 |
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RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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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 |
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1799135524605132800 |