Rodent blood-stage Plasmodium survive in dendritic cells that infect naive mice

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 108; no. 27; pp. 11205 - 11210
• Main Authors: Wykes, Michelle N, Kay, Jason G, Manderson, Anthony, Liu, Xue Q, Brown, Darren L, Richard, Derek J, Wipasa, Jiraprapa, Jiang, Suhua H, Jones, Malcolm K, Janse, Chris J, Waters, Andrew P, Pierce, Susan K, Miller, Louis H, Stow, Jennifer L, Good, Michael F
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 05.07.2011; National Acad Sciences
• Subjects: Animals; Animals, Genetically Modified; Antigens, CD - metabolism; Biological Sciences; Blood; Cell culture; confocal microscopy; Dendritic cells; Dendritic Cells - immunology; Dendritic Cells - parasitology; Dendritic Cells - ultrastructure; erythrocytes; Erythrocytes - parasitology; Female; Gene expression; genetically modified organisms; Green Fluorescent Proteins - genetics; hepatocytes; Humans; immunity; Infections; Malaria; Malaria - parasitology; Membrane Glycoproteins - metabolism; Merozoites; Mice; Mice, Inbred C57BL; Microscopy, Electron, Transmission; Parasite hosts; Parasitemia; Parasites; Parasitic protozoa; Parasitism; Plasmodium - growth & development; Plasmodium - immunology; Plasmodium - pathogenicity; Plasmodium berghei - genetics; Plasmodium berghei - growth & development; Plasmodium berghei - pathogenicity; Plasmodium chabaudi - pathogenicity; Plasmodium falciparum; Plasmodium malariae; Plasmodium ovale; Plasmodium vivax; Plasmodium yoelii - pathogenicity; Recombinant Proteins - genetics; Rodents; Schizonts; Spleen; vaccine development; Virulence
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1108579108

Plasmodium spp. parasites cause malaria in 300 to 500 million individuals each year. Disease occurs during the blood-stage of the parasite's life cycle, where the parasite is thought to replicate exclusively within erythrocytes. Infected individuals can also suffer relapses after several years, from Plasmodium vivax and Plasmodium ovale surviving in hepatocytes. Plasmodium falciparum and Plasmodium malariae can also persist after the original bout of infection has apparently cleared in the blood, suggesting that host cells other than erythrocytes (but not hepatocytes) may harbor these blood-stage parasites, thereby assisting their escape from host immunity. Using blood stage transgenic Plasmodium berghei-expressing GFP (PbGFP) to track parasites in host cells, we found that the parasite had a tropism for CD317⁺ dendritic cells. Other studies using confocal microscopy, in vitro cultures, and cell transfer studies showed that blood-stage parasites could infect, survive, and replicate within CD317⁺ dendritic cells, and that small numbers of these cells released parasites infectious for erythrocytes in vivo. These data have identified a unique survival strategy for blood-stage Plasmodium, which has significant implications for understanding the escape of Plasmodium spp. from immune-surveillance and for vaccine development.