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In Vivo Approaches Reveal a Key Role for DCs in CD4+ T Cell Activation and Parasite Clearance during the Acute Phase of Experimental Blood-Stage Malaria

2015-02-06Journal article Open access
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dc.contributor.authorBorges da Silva, Henrique
dc.contributor.authorFonseca, Raíssa
dc.contributor.authorCassado, Alexandra dos Anjos
dc.contributor.authorMachado de Salles, Érika
dc.contributor.authorde Menezes, Maria Nogueira
dc.contributor.authorLanghorne, Jean
dc.contributor.authorPerez, Katia Regina
dc.contributor.authorCuccovia, Iolanda Midea
dc.contributor.authorRyffel, Bernhard
dc.contributor.authorBarreto, Vasco M.
dc.contributor.authorMarinho, Cláudio Romero Farias
dc.contributor.authorBoscardin, Silvia Beatriz
dc.contributor.authorÁlvarez, José Maria
dc.contributor.authorD’Império-Lima, Maria Regina
dc.contributor.authorTadokoro, Carlos Eduardo
dc.date.accessioned2015-10-13T10:09:28Z
dc.date.available2015-10-13T10:09:28Z
dc.date.issued2015-02-06
dc.description.abstractDendritic cells (DCs) are phagocytes that are highly specialized for antigen presentation. Heterogeneous populations of macrophages and DCs form a phagocyte network inside the red pulp (RP) of the spleen, which is a major site for the control of blood-borne infections such as malaria. However, the dynamics of splenic DCs during Plasmodium infections are poorly understood, limiting our knowledge regarding their protective role in malaria. Here, we used in vivo experimental approaches that enabled us to deplete or visualize DCs in order to clarify these issues. To elucidate the roles of DCs and marginal zone macrophages in the protection against blood-stage malaria, we infected DTx (diphtheria toxin)-treated C57BL/6.CD11c-DTR mice, as well as C57BL/6 mice treated with low doses of clodronate liposomes (ClLip), with Plasmodium chabaudi AS (Pc) parasites. The first evidence suggesting that DCs could contribute directly to parasite clearance was an early effect of the DTx treatment, but not of the ClLip treatment, in parasitemia control. DCs were also required for CD4+ T cell responses during infection. The phagocytosis of infected red blood cells (iRBCs) by splenic DCs was analyzed by confocal intravital microscopy, as well as by flow cytometry and immunofluorescence, at three distinct phases of Pc malaria: at the first encounter, at pre-crisis concomitant with parasitemia growth and at crisis when the parasitemia decline coincides with spleen closure. In vivo and ex vivo imaging of the spleen revealed that DCs actively phagocytize iRBCs and interact with CD4+ T cells both in T cell-rich areas and in the RP. Subcapsular RP DCs were highly efficient in the recognition and capture of iRBCs during pre-crisis, while complete DC maturation was only achieved during crisis. These findings indicate that, beyond their classical role in antigen presentation, DCs also contribute to the direct elimination of iRBCs during acute Plasmodium infection.pt_PT
dc.description.sponsorshipSão Paulo Research Foundation grants: (2011/24038-1 [MRDL], 2009/08559-1 [HBdS], CAPES/IGC 04/ 2012 [MRDL, CET]).pt_PT
dc.identifier10.1371/journal.ppat.1004598
dc.identifier.citationBorges da Silva H, Fonseca R, Cassado AdA, Machado de Salles Érika, de Menezes MN, Langhorne J, et al. (2015) In Vivo Approaches Reveal a Key Role for DCs in CD4+ T Cell Activation and Parasite Clearance during the Acute Phase of Experimental Blood-Stage Malaria. PLoS Pathog 11(2): e1004598. doi:10.1371/journal.ppat.1004598pt_PT
dc.identifier.doi10.1371/journal.ppat.1004598
dc.identifier.urihttp://hdl.handle.net/10400.7/390
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherPLOSpt_PT
dc.relationGeneration of new transgenic animals for in vivo tracking of Regulatory T cells
dc.relation.publisherversionhttp://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1004598pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectT cellspt_PT
dc.subjectMalariapt_PT
dc.subjectParasitemiapt_PT
dc.titleIn Vivo Approaches Reveal a Key Role for DCs in CD4+ T Cell Activation and Parasite Clearance during the Acute Phase of Experimental Blood-Stage Malariapt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleGeneration of new transgenic animals for in vivo tracking of Regulatory T cells
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FEBB-BIO%2F115514%2F2009/PT
oaire.citation.endPage24pt_PT
oaire.citation.issue2pt_PT
oaire.citation.startPage1pt_PT
oaire.citation.titlePlos Pathogenspt_PT
oaire.citation.volume11pt_PT
oaire.fundingStream3599-PPCDT
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isProjectOfPublication34ec30ee-f065-4b38-8a34-9c3c95346f02
relation.isProjectOfPublication.latestForDiscovery34ec30ee-f065-4b38-8a34-9c3c95346f02

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