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dc.contributor.authorda Silva, HB
dc.contributor.authorFonseca, R
dc.contributor.authorCassado, ADA
dc.contributor.authorde Salles, EM
dc.contributor.authorde Menezes, MN
dc.contributor.authorLanghorne, J
dc.contributor.authorPerez, KR
dc.contributor.authorCuccovia, IM
dc.contributor.authorRyffel, B
dc.contributor.authorBarreto, VM
dc.contributor.authorFarias Marinho, CR
dc.contributor.authorBoscardin, SB
dc.contributor.authorAlvarez, JM
dc.contributor.authorD'Imperio-Lima, MR
dc.contributor.authorTadokoro, CE
dc.date.accessioned2020-12-17T03:28:39Z
dc.date.available2020-12-17T03:28:39Z
dc.date.issued2015-02-01
dc.identifierpii: PPATHOGENS-D-13-03331
dc.identifier.citationda Silva, H. B., Fonseca, R., Cassado, A. D. A., de Salles, E. M., de Menezes, M. N., Langhorne, J., Perez, K. R., Cuccovia, I. M., Ryffel, B., Barreto, V. M., Farias Marinho, C. R., Boscardin, S. B., Alvarez, J. M., D'Imperio-Lima, M. R. & Tadokoro, C. E. (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 PATHOGENS, 11 (2), https://doi.org/10.1371/journal.ppat.1004598.
dc.identifier.issn1553-7366
dc.identifier.urihttp://hdl.handle.net/11343/254903
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.
dc.languageEnglish
dc.publisherPUBLIC LIBRARY SCIENCE
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
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 Malaria
dc.typeJournal Article
dc.identifier.doi10.1371/journal.ppat.1004598
melbourne.affiliation.departmentMicrobiology and Immunology
melbourne.source.titlePLoS Pathogens
melbourne.source.volume11
melbourne.source.issue2
dc.rights.licenseCC BY
melbourne.elementsid1325982
melbourne.contributor.authorFonseca, Raissa
melbourne.contributor.authorNogueira de Menezes, Maria
dc.identifier.eissn1553-7374
melbourne.accessrightsOpen Access


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