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Heme catabolism by heme oxygenase-1 confers host resistance to Mycobacterium infection

2013-07Journal article Open access
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dc.contributor.authorSilva-Gomes, Sandro
dc.contributor.authorAppelberg, Rui
dc.contributor.authorLarsen, Rasmus
dc.contributor.authorSoares, Miguel Parreira
dc.contributor.authorGomes, Maria Salomé
dc.date.accessioned2015-11-09T18:05:14Z
dc.date.available2015-11-09T18:05:14Z
dc.date.issued2013-07
dc.description.abstractHeme 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) 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, an effect mimicked by exogenous heme administration to M. avium-infected wild-type M in vitro or to mice in vivo. In conclusion, HO-1 prevents the cytotoxic effect of heme in M, contributing critically to host resistance to Mycobacterium infection.pt_PT
dc.description.sponsorshipEuropean Community 6th Framework grant: (LSH-2005-1.2.5-1), FCT fellowships: (SFRH/BD/29257/2006, SFRH/BPD/25436/2005), Instituto Gulbenkian de Ciência, Universidade do Minho, ICBAS.pt_PT
dc.identifier10.1128/IAI.00251-13
dc.identifier.citationHeme Catabolism by Heme Oxygenase-1 Confers Host Resistance to Mycobacterium Infection Sandro Silva-Gomes, Rui Appelberg, Rasmus Larsen, Miguel Parreira Soares, and Maria Salomé Gomes Infect. Immun. July 2013 81:7 2536-2545; Accepted manuscript posted online 29 April 2013, doi:10.1128/IAI.00251-13pt_PT
dc.identifier.doi10.1128/IAI.00251-13
dc.identifier.doi10.1128/IAI.00251-13
dc.identifier.urihttp://hdl.handle.net/10400.7/480
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherAmerican Society for Microbiologypt_PT
dc.relationRole of heme oxygenase 1 in the infection by macrophage intracellular pathogens
dc.relationTissue Damage Control Regulates The Pathogenesis of Immune Mediated Inflammatory Diseases
dc.relationModulation of programmed cell death by cellular free heme
dc.relation.publisherversionhttp://iai.asm.org/content/81/7/2536.longpt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectHemept_PT
dc.subjectheme oxygenase-1pt_PT
dc.subjectDisease Resistancept_PT
dc.subjectMycobacterium infectionpt_PT
dc.subjectTuberculosispt_PT
dc.titleHeme catabolism by heme oxygenase-1 confers host resistance to Mycobacterium infectionpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleRole of heme oxygenase 1 in the infection by macrophage intracellular pathogens
oaire.awardTitleTissue Damage Control Regulates The Pathogenesis of Immune Mediated Inflammatory Diseases
oaire.awardTitleModulation of programmed cell death by cellular free heme
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/POCI/POCI%2FSAU-IMI%2F56578%2F2004/PT
oaire.awardURIinfo:eu-repo/grantAgreement/EC/FP7/294709/EU
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FBIA-BCM%2F101311%2F2008/PT
oaire.citation.endPage2545pt_PT
oaire.citation.issue7pt_PT
oaire.citation.startPage2536pt_PT
oaire.citation.titleInfection and Immunitypt_PT
oaire.citation.volume81pt_PT
oaire.fundingStreamPOCI
oaire.fundingStreamFP7
oaire.fundingStream3599-PPCDT
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100008530
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameEuropean Commission
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isProjectOfPublicationdac9e839-29c8-4e65-bfc7-ec29701ec9a9
relation.isProjectOfPublication370f9aad-c4ef-4e35-b754-edc840dc6b5e
relation.isProjectOfPublication07a35b73-a323-4c2c-b7af-d0d76fd04235
relation.isProjectOfPublication.latestForDiscovery370f9aad-c4ef-4e35-b754-edc840dc6b5e

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