Interaction of Mouse Dendritic Cells and Malaria-Infected Erythrocytes: Uptake, Maturation, and Antigen Presentation

Abstract

Consistent with their seminal role in detecting infection, both mouse bone marrow-derived and splenic CD11c+ dendritic cells (DCs) exhibited higher levels of uptake of Plasmodium chabaudi-parasitized RBCs (pRBCs) than of noninfected RBCs (nRBCs) as determined by our newly developed flow cytometric technique using the dye CFSE to label RBCs before coculture with DCs. To confirm that expression of CFSE by CD11c+ cells following coculture with CFSE-labeled pRBCs represents internalization of pRBC by DCs, we showed colocalization of CFSE-labeled pRBCs and PE-labeled CD11c+ DCs by confocal fluorescence microscopy. Treatment of DCs with cytochalasin D significantly inhibited the uptake of pRBCs, demonstrating that uptake is an actin-dependent phagocytic process. The uptake of pRBCs by splenic CD11c+ DCs was significantly enhanced after infection in vivo and was associated with the induction of DC maturation, IL-12 production, and stimulation of CD4+ T cell proliferation and IFN-γ production. These results suggest that DCs selectively phagocytose pRBCs and present pRBC-derived Ags to CD4+ T cells, thereby promoting development of protective Th1-dependent immune responses to blood-stage malaria infection.

Involvement of CD8+ T cells in protective immunity against murine blood‐stage infection with Plasmodium yoelii 17XL strain

“…Taken together with our observation that the numbers of activated CD8 1 T cells increased after infection with PyL, antigens derived from malaria parasites must be presented on MHC class I molecules on APC including macrophages. The activation mechanism of CD8 1 T cells may be explained by cross-presentation of APC that have engulfed pRBC as other particle antigens [26].…”

“…The macrophage phagocytosis assay was a modification of a previous method [26]. To stain pRBC or normal RBC, cells (10 7 cells/mL) were incubated with 10 mM CFSE (Molecular Probes, CA, USA) in PBS for 15 min at 371C.…”

Therapeutical targeting of nucleic acid-sensing Toll-like receptors prevents experimental cerebral malaria

“…4C, Lower). Nucleic acid-sensing TLRs (e.g., TLR9, TLR7) are highly expressed on dendritic cells (DCs) and were shown to be activated by Plasmodium products that play a relevant role in malaria pathogenesis (18,30,31). We thus sought to identify the effect of E6446 on cytokines produced by myeloid CD11c + MHCII + DCs using a flow cytometry (FACS) assay for intracellular cytokine staining.…”

Malaria Parasites Require TLR9 Signaling for Immune Evasion by Activating Regulatory T Cells

“…Parasite-derived molecules usually contact DCs after being processed in phago-endosomes (27). In contrast, pRBCs express some molecules derived from the parasites on their surfaces, and this enables parasites to interact with the surfaces of DCs without phagocytosis (3).…”