Expansion of host cellular niche can drive adaptation of a zoonotic malaria parasite to humans

Caeul Lim, Elsa Hansen, Tiffany M. DeSimone, Yovany Moreno, Klara Junker, Amy Bei, Carlo Brugnara, Caroline O. Buckee () and Manoj T. Duraisingh ()
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Caeul Lim: Harvard School of Public Health
Elsa Hansen: Center for Communicable Disease Dynamics, Harvard School of Public Health
Tiffany M. DeSimone: Harvard School of Public Health
Yovany Moreno: Harvard School of Public Health
Klara Junker: Harvard School of Public Health
Amy Bei: Harvard School of Public Health
Carlo Brugnara: Children’s Hospital Boston
Caroline O. Buckee: Center for Communicable Disease Dynamics, Harvard School of Public Health
Manoj T. Duraisingh: Harvard School of Public Health

Nature Communications, 2013, vol. 4, issue 1, 1-9

Abstract: Abstract 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.

Date: 2013
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DOI: 10.1038/ncomms2612

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