Intravital imaging shows a key role for splenic DCs in acute malaria for CD4+ T cell activation and parasite clearance (MPF6P.747)

Abstract

Abstract Heterogeneous populations of macrophages and dendritic cells (DCs) form a complex phagocyte network inside the red pulp (RP) of the spleen, which is a major site for the control of blood-borne infectious diseases, such as malaria. However, the dynamics of splenic DCs during Plasmodium infections are poorly understood, obscuring our knowledge about the protective role of these cells in malaria. To address this issue, the phagocytosis of infected red blood cells (iRBCs) by splenic DCs was quantified by confocal intravital microscopy, as well as by flow cytometry and immunofluorescence, in three distinct phases of blood-stage Plasmodium chabaudi malaria: at the first encounter, at pre-crisis concomitant with parasitemia growth and at crisis, when the parasitemia decline coincides with spleen closure. The in vivo and ex vivo imaging of the spleen during the early infection shows that DCs phagocytize iRBCs and interact with CD4+ T cells in CD4+ T cell-rich areas and the RP. This analysis also reveals that the RP DC population maintains the ability to phagocytize iRBCs during pre-crisis stages and greatly contributes to parasite control. These findings add novel information to the immunology field and demonstrate that in vivo imaging can help to unravel the protective mechanisms against malaria.