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

• DOI: 10.1371/journal.ppat.1004598
• Publication Date: 2015-02-06T22:12:03Z
• Authors: Henrique Borges d...; Raíssa Fonseca; Alexandra dos Anj...; Érika Machado de ...; Maria Nogueira de...; Jean Langhorne; Katia Regina Perez; Iolanda Midea Cuc...; Bernhard Ryffel; Vasco M. Barreto; Cláudio Romero Fa...; Silvia Beatriz Bo...; José Maria Álvarez; Maria Regina D’Im...; Carlos Eduardo Ta...
• Keywords: CD11c; Red pulp; Mononuclear phagocyte system; Ex vivo

Dendritic cells (DCs) are phagocytes that highly specialized for antigen presentation. Heterogeneous populations of macrophages and DCs form a phagocyte network inside the red pulp (RP) spleen, which is major site control blood-borne infections such as malaria. However, dynamics splenic during Plasmodium poorly understood, limiting our knowledge regarding their protective role in Here, we used vivo experimental approaches enabled us to deplete or visualize order clarify these issues. To elucidate roles marginal zone protection against blood-stage malaria, infected DTx (diphtheria toxin)-treated C57BL/6.CD11c-DTR mice, well C57BL/6 mice treated with low doses clodronate liposomes (ClLip), chabaudi AS (Pc) parasites. The first evidence suggesting could contribute directly parasite clearance was an early effect treatment, but not ClLip parasitemia control. were also required CD4+ T cell responses infection. phagocytosis blood (iRBCs) by analyzed confocal intravital microscopy, flow cytometry immunofluorescence, at three distinct phases Pc malaria: encounter, pre-crisis concomitant growth crisis when decline coincides spleen closure. In ex imaging revealed actively phagocytize iRBCs interact both cell-rich areas RP. Subcapsular RP efficient recognition capture pre-crisis, while complete DC maturation only achieved crisis. These findings indicate that, beyond classical presentation, direct elimination acute