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

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

Autor Silva, Henrique Borges da Google Scholar
Fonseca, Raissa Google Scholar
Cassado, Alexandra dos Anjos Google Scholar
Salles, Erika Machado de Google Scholar
Menezes, Maria Nogueira de Google Scholar
Langhorne, Jean Google Scholar
Perez, Katia Regina Autor UNIFESP Google Scholar
Cuccovia, Iolanda Midea Google Scholar
Ryffel, Bernhard Google Scholar
Barreto, Vasco M. Google Scholar
Farias Marinho, Claudio Romero Google Scholar
Boscardin, Silvia Beatriz Google Scholar
Alvarez, Jose Maria Google Scholar
D'Imperio-Lima, Maria Regina Google Scholar
Tadokoro, Carlos Eduardo Google Scholar
Instituição Universidade de São Paulo (USP)
Inst Gulbenkian Ciencias
Charing Cross Sunley Med Res Ctr
Universidade Federal de São Paulo (UNIFESP)
Univ Orleans
Resumo Dendritic 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 (CILip), 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 CILip 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.
Idioma Inglês
Financiador Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Fundacao para a Ciencia e Tecnologia
Número do financiamento FAPESP: 2011/24038-1
FAPESP: 2009/08559-1
CAPES: 04/2012
Fundacao para a Ciencia e Tecnologia: PTDC/EBB-BIO/115514/2009
Data de publicação 2015-02-01
Publicado em Plos Pathogens. San Francisco: Public Library Science, v. 11, n. 2, 24 p., 2015.
ISSN 1553-7366 (Sherpa/Romeo, fator de impacto)
Publicador Public Library Science
Extensão 24
Fonte http://dx.doi.org/10.1371/journal.ppat.1004598
Direito de acesso Acesso aberto Open Access
Tipo Artigo
Web of Science WOS:000352083400006
Endereço permanente http://repositorio.unifesp.br/handle/11600/38663

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