Increased susceptibility to Mycobacterium avium in hemochromatosis protein HFE-deficient mice
Autor(a) principal: | |
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Data de Publicação: | 2008 |
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/10216/69108 |
Resumo: | Mycobacterium avium is an opportunistic infectious agent in immunocompromised patients, living inside macrophage phagosomes. As for other mycobacterial species, iron availability is a critical factor for M. avium survival and multiplication. Indeed, an association between host secondary iron overload and increased susceptibility to these mycobacteria is generally acknowledged. However, studies on the impact of primary iron overload on M. avium infection have not been performed. In this work, we used animal models of primary iron overload that mimic the human disease hereditary hemochromatosis. This pathology is characterized by increased serum transferrin saturation with iron deposition in parenchymal cells, mainly in the liver, and is most often associated with mutations in the gene encoding the molecule HFE. In this paper, we demonstrate that mice of two genetically determined primary iron overload phenotypes, Hfe(-/-) and beta 2m(-/-), show an increased susceptibility to experimental infection with M. avium and that during infection these animals accumulate iron inside granuloma macrophages. beta 2m(-/-) mice were found to be more susceptible than Hfe(-/-) mice, but depleting Hfe(-/-) mice of CD8(+) cells had no effect on resistance to infection. Overall, our results suggest that serum iron, rather than total liver iron, levels have a considerable impact on susceptibility to M. avium infection. |
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Increased susceptibility to Mycobacterium avium in hemochromatosis protein HFE-deficient miceInfecções, Medicina básicaInfections, Basic medicineMycobacterium avium is an opportunistic infectious agent in immunocompromised patients, living inside macrophage phagosomes. As for other mycobacterial species, iron availability is a critical factor for M. avium survival and multiplication. Indeed, an association between host secondary iron overload and increased susceptibility to these mycobacteria is generally acknowledged. However, studies on the impact of primary iron overload on M. avium infection have not been performed. In this work, we used animal models of primary iron overload that mimic the human disease hereditary hemochromatosis. This pathology is characterized by increased serum transferrin saturation with iron deposition in parenchymal cells, mainly in the liver, and is most often associated with mutations in the gene encoding the molecule HFE. In this paper, we demonstrate that mice of two genetically determined primary iron overload phenotypes, Hfe(-/-) and beta 2m(-/-), show an increased susceptibility to experimental infection with M. avium and that during infection these animals accumulate iron inside granuloma macrophages. beta 2m(-/-) mice were found to be more susceptible than Hfe(-/-) mice, but depleting Hfe(-/-) mice of CD8(+) cells had no effect on resistance to infection. Overall, our results suggest that serum iron, rather than total liver iron, levels have a considerable impact on susceptibility to M. avium infection.20082008-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10216/69108eng0019-956710.1128/iai.00612-08Sandra Gomes PereiraPedro Nuno RodriguesRui AppelbergMaria 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:RCAAP2023-11-29T14:46:11Zoai:repositorio-aberto.up.pt:10216/69108Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T00:08:06.576816Repositório 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 |
Increased susceptibility to Mycobacterium avium in hemochromatosis protein HFE-deficient mice |
title |
Increased susceptibility to Mycobacterium avium in hemochromatosis protein HFE-deficient mice |
spellingShingle |
Increased susceptibility to Mycobacterium avium in hemochromatosis protein HFE-deficient mice Sandra Gomes Pereira Infecções, Medicina básica Infections, Basic medicine |
title_short |
Increased susceptibility to Mycobacterium avium in hemochromatosis protein HFE-deficient mice |
title_full |
Increased susceptibility to Mycobacterium avium in hemochromatosis protein HFE-deficient mice |
title_fullStr |
Increased susceptibility to Mycobacterium avium in hemochromatosis protein HFE-deficient mice |
title_full_unstemmed |
Increased susceptibility to Mycobacterium avium in hemochromatosis protein HFE-deficient mice |
title_sort |
Increased susceptibility to Mycobacterium avium in hemochromatosis protein HFE-deficient mice |
author |
Sandra Gomes Pereira |
author_facet |
Sandra Gomes Pereira Pedro Nuno Rodrigues Rui Appelberg Maria Salome Gomes |
author_role |
author |
author2 |
Pedro Nuno Rodrigues Rui Appelberg Maria Salome Gomes |
author2_role |
author author author |
dc.contributor.author.fl_str_mv |
Sandra Gomes Pereira Pedro Nuno Rodrigues Rui Appelberg Maria Salome Gomes |
dc.subject.por.fl_str_mv |
Infecções, Medicina básica Infections, Basic medicine |
topic |
Infecções, Medicina básica Infections, Basic medicine |
description |
Mycobacterium avium is an opportunistic infectious agent in immunocompromised patients, living inside macrophage phagosomes. As for other mycobacterial species, iron availability is a critical factor for M. avium survival and multiplication. Indeed, an association between host secondary iron overload and increased susceptibility to these mycobacteria is generally acknowledged. However, studies on the impact of primary iron overload on M. avium infection have not been performed. In this work, we used animal models of primary iron overload that mimic the human disease hereditary hemochromatosis. This pathology is characterized by increased serum transferrin saturation with iron deposition in parenchymal cells, mainly in the liver, and is most often associated with mutations in the gene encoding the molecule HFE. In this paper, we demonstrate that mice of two genetically determined primary iron overload phenotypes, Hfe(-/-) and beta 2m(-/-), show an increased susceptibility to experimental infection with M. avium and that during infection these animals accumulate iron inside granuloma macrophages. beta 2m(-/-) mice were found to be more susceptible than Hfe(-/-) mice, but depleting Hfe(-/-) mice of CD8(+) cells had no effect on resistance to infection. Overall, our results suggest that serum iron, rather than total liver iron, levels have a considerable impact on susceptibility to M. avium infection. |
publishDate |
2008 |
dc.date.none.fl_str_mv |
2008 2008-01-01T00:00:00Z |
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/10216/69108 |
url |
https://hdl.handle.net/10216/69108 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
0019-9567 10.1128/iai.00612-08 |
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 |
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 |
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1799136006556876801 |