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HGF Secreted by Activated Kupffer Cells Induces Apoptosis of Plasmodium-Infected Hepatocytes

2017-02-06Journal article Open access
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dc.contributor.authorGonçalves, Lígia Antunes
dc.contributor.authorRodo, Joana
dc.contributor.authorRodrigues-Duarte, Lurdes
dc.contributor.authorde Moraes, Luciana Vieira
dc.contributor.authorPenha-Gonçalves, Carlos
dc.date.accessioned2017-02-23T14:55:09Z
dc.date.available2017-02-23T14:55:09Z
dc.date.issued2017-02-06
dc.descriptionThis deposit is composed by the main article plus the supplementary materials of the publication
dc.description.abstractMalaria liver stage infection is an obligatory parasite development step and represents a population bottleneck in Plasmodium infections, providing an advantageous target for blocking parasite cycle progression. Parasite development inside hepatocytes implies a gross cellular insult evoking innate host responses to counteract intra-hepatocytic infection. Using primary hepatocyte cultures, we investigated the role of Kupffer cell-derived hepatocyte growth factor (HGF) in malaria liver stage infection. We found that Kupffer cells from Plasmodium-infected livers produced high levels of HGF, which trigger apoptosis of infected hepatocytes through a mitochondrial-independent apoptosis pathway. HGF action in infected hepatocyte primary cultures results in a potent reduction of parasite yield by specifically sensitizing hepatocytes carrying established parasite exo-erythrocytic forms to undergo apoptosis. This apoptosis mechanism is distinct from cell death that is spontaneously induced in infected cultures and is governed by Fas signaling modulation through a mitochondrial-dependent apoptosis pathway. This work indicates that HGF and Fas signaling pathways are part of an orchestrated host apoptosis response that occurs during malaria liver stage infection, decreasing the success of infection of individual hepatocytes. Our results raise the hypothesis that paracrine signals derived from Kupffer cell activation are implicated in directing death of hepatocytes infected with the malaria parasite.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationGonçalves LA, Rodo J, Rodrigues- Duarte L, de Moraes LV and Penha-Gonçalves C (2017) HGF Secreted by Activated Kupffer Cells Induces Apoptosis of Plasmodium- Infected Hepatocytes. Front. Immunol. 8:90. doi: 10.3389/fimmu.2017.00090pt_PT
dc.identifier.doi10.3389/fimmu.2017.00090pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.7/737
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherFrontiers Mediapt_PT
dc.relationGENETIC DISSECTION OF A MALARIA LIVER STAGE RESISTANCE LOCUS BELR1
dc.relationMATERNAL EFFECTS IN AUTOIMMUNITY MOUSE MODELS
dc.relationMALARIA: PATHOGENESIS MECHANISMS IN THE ERYTRHOCYTIC STAGE
dc.relationINFLAMMATORY AND IMMUNOLOGICAL COMPONENTS IN MURINE PREGNANCY ASSOCIATED MALARIA
dc.relation.publisherversionhttp://journal.frontiersin.org/article/10.3389/fimmu.2017.00090/fullpt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectPlasmodiumpt_PT
dc.subjectKupffer cellspt_PT
dc.subjecthepatocytespt_PT
dc.subjectHGFpt_PT
dc.subjectapoptosispt_PT
dc.subjectmalariapt_PT
dc.subjectliverpt_PT
dc.titleHGF Secreted by Activated Kupffer Cells Induces Apoptosis of Plasmodium-Infected Hepatocytespt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleGENETIC DISSECTION OF A MALARIA LIVER STAGE RESISTANCE LOCUS BELR1
oaire.awardTitleMATERNAL EFFECTS IN AUTOIMMUNITY MOUSE MODELS
oaire.awardTitleMALARIA: PATHOGENESIS MECHANISMS IN THE ERYTRHOCYTIC STAGE
oaire.awardTitleINFLAMMATORY AND IMMUNOLOGICAL COMPONENTS IN MURINE PREGNANCY ASSOCIATED MALARIA
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/POCI/POCI%2FSAU-IMI%2F61057%2F2004/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBD%2F44208%2F2008/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBD%2F29862%2F2006/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBD%2F33566%2F2008/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBPD%2F44486%2F2008/PT
oaire.citation.endPage11pt_PT
oaire.citation.startPage1pt_PT
oaire.citation.titleFrontiers in Immunologypt_PT
oaire.citation.volume8pt_PT
oaire.fundingStreamPOCI
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project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
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