title: Expansion of host cellular niche can drive adaptation of a zoonotic malaria parasite to humans.
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.
authors.affiliation: Department of Immunology & Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA.
authors.forename: Caeul
authors.initials: C
authors.lastname: Lim
authors.affiliation: Center for Communicable Disease Dynamics, Harvard School of Public Health, MA, 02115, USA.
authors.forename: Elsa
authors.initials: E
authors.lastname: Hansen
authors.affiliation: Department of Immunology & Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA.
authors.forename: Tiffany M
authors.initials: TM
authors.lastname: DeSimone
authors.affiliation: Department of Immunology & Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA.
authors.forename: Yovany
authors.initials: Y
authors.lastname: Moreno
authors.affiliation: Department of Immunology & Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA.
authors.forename: Klara
authors.initials: K
authors.lastname: Junker
authors.affiliation: Department of Immunology & Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA.
authors.forename: Amy
authors.initials: A
authors.lastname: Bei
authors.affiliation: Department of Laboratory Medicine, Children's Hospital Boston, Boston, MA 02115, USA.
authors.forename: Carlo
authors.initials: C
authors.lastname: Brugnara
authors.affiliation: Center for Communicable Disease Dynamics, Harvard School of Public Health, MA, 02115, USA.|Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA.
authors.forename: Caroline O
authors.initials: CO
authors.lastname: Buckee
authors.affiliation: Department of Immunology & Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA.
authors.forename: Manoj T
authors.initials: MT
authors.lastname: Duraisingh
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D004912:Erythrocytes / Q000469:parasitology; D006801:Humans; D008253:Macaca mulatta; D016790:Plasmodium knowlesi / Q000502:physiology*; D015047:Zoonoses
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