Journal
NATURE COMMUNICATIONS
Volume 4, Issue -, Pages -Publisher
NATURE RESEARCH
DOI: 10.1038/ncomms2612
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Funding
- Bill and Melinda Gates Foundation
- National Institutes of Health [R01AI091787]
- National Institute of General Medical Sciences [U54GM088558]
- Louis-Berlinguet Program Postdoctoral Research Scholarship in Genomics-Fonds de recherche du Quebec, Nature et technologies
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The macaque malaria parasite Plasmodium knowlesi has recently emerged as an important zoonosis in Southeast Asia. Infections are typically mild but can cause severe disease, achieving parasite densities similar to fatal Plasmodium falciparum infections. Here we show that a primate-adapted P. knowlesi parasite proliferates poorly in human blood due to a strong preference for young red blood cells (RBCs). We establish a continuous in vitro culture system by using human blood enriched for young cells. Mathematical modelling predicts that parasite adaptation for invasion of older RBCs is a likely mechanism leading to high parasite densities in clinical infections. Consistent with this model, we find that P. knowlesi can adapt to invade a wider age range of RBCs, resulting in proliferation in normal human blood. Such cellular niche expansion may increase pathogenesis in humans and will be a key feature to monitor as P. knowlesi emerges in human populations.
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