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. We show that a primate-adapted P. knowlesi parasite proliferates poorly in human blood due to a strong preference for young red blood cells. We establish a continuous in vitro culture system by using human blood enriched for young cells. Mathematical modeling predicts that parasite adaptation for invasion of older red blood cells 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 red blood cells, 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.
Expansion of host cellular niche can drive adaptation of a zoonotic malaria parasite to humans
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[Article Type] Article
[Source] PMC
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