Efficient phagosomal maturation and degradation of Plasmodium-infected erythrocytes by dendritic cells and macrophages

Abstract

Dendritic cells (DC) and macrophages phagocytose pathogens and degrade them in their phagosomes to allow for proper presentation of foreign antigens to other cells of the immune system. The Plasmodium parasite, causative agent of malaria, infects RBC that are phagocytosed by DC and macrophages during the course of infection. Under specific conditions, the functionality of these cells can be affected by phagocytosis of Plasmodium-infected RBC. We investigated whether phagosomal maturation and degradation of Plasmodium yoelii-infected RBC in phagosomes is affected in DC and macrophages. We show that recruitment of the phagolysosomal marker Lamp-1 and of MHC-II, as well as acidification of phagosomes, was achieved in a timely manner. Using P. yoelii-infected RBC labelled with a fluorescent dye or transgenic green fluorescent protein (GFP)-expressing parasites, we found a gradual, rapid decrease in the phagosome fluorescence signal, indicating that P. yoelii-infected RBC are efficiently degraded in macrophages and DC. We also observed that pre-incubation of DC with infected RBC did not affect phagosomal maturation of newly internalized P. yoelii-infected RBC. In conclusion, after phagocytosis, Plasmodium-infected RBC are degraded by DC and macrophages, suggesting that the process of phagosomal maturation is effectively completed in malaria.

Dual Engagement of the NLRP3 and AIM2 Inflammasomes by Plasmodium-Derived Hemozoin and DNA during Malaria

“…This Hz is presumably due to the phagocytosis and degradation of parasites that contained Hz (Bettiol et al, 2010; Ing et al, 2006; McGilvray et al, 2000) in addition to the uptake of any free Hz that may be in the vasculature. Plasmodium berghei infected RBCs (iRBCs) often have visible Hz within them when stained with Giemsa.…”

Deploying FLAREs to Visualize Functional Outcomes of Host—Pathogen Encounters

“…In experiments with recombinant Escherichia coli , DsRed degradation within Dictiostylium discoideum phagosomes occurred with a half-life of approximately 45 minutes [ 15 ]. Consistent with these results, the fluorescence signal in GFP-expressing Plasmodium yoelii -infected red blood cells was degraded with a half-life of 30–60 minutes in murine macrophage and dendritic cell phagosomes in vitro [ 23 ]. The mechanism by which DsRed and other genetically encoded fluorophores are quenched and degraded within mammalian phagosomes remains poorly defined.…”

Buffer-Optimized High Gradient Magnetic Separation: Target Cell Capture Efficiency is Predicted by Linear Bead-Capture Theory

“…Mitotic indices of CD3-positive cells were highest when stimulated with PHA-L, while stimulation with iRBCs resulted in lower, but still significant, mitosis. The latter does not seem surprising given the entirely different mechanisms of stimulation: PHA-L directly recruits T lymphocytes to undergo mitosis [23] whereas iRBCs are phagocytosed by monocytes and by antigens presented to T lymphocytes [24].…”