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Accounting for red blood cell accessibility reveals distinct invasion strategies in Plasmodium falciparum strains

Francisco Cai, Tiffany M. DeSimone, Elsa Hansen, Cameron V. Jennings, Amy K. Bei, Ambroise D. Ahouidi, Souleymane Mboup, Manoj T. Duraisingh, Caroline O. Buckee
doi: https://doi.org/10.1101/626044
Francisco Cai
Center for Communicable Disease Dynamics, Department of Epidemiology, Harvard TH Chan School of Public Health, Boston, USA
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Tiffany M. DeSimone
Department of Immunology and Infectious Diseases, Harvard TH Chan School of Public Health, Boston, USA
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Elsa Hansen
Center for Communicable Disease Dynamics, Department of Epidemiology, Harvard TH Chan School of Public Health, Boston, USA
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Cameron V. Jennings
Department of Immunology and Infectious Diseases, Harvard TH Chan School of Public Health, Boston, USA
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Amy K. Bei
Department of Immunology and Infectious Diseases, Harvard TH Chan School of Public Health, Boston, USA
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Ambroise D. Ahouidi
Laboratory of Bacteriology and Virology, Le Dantec Hospital, Cheikh Anta Diop University, Dakar, Senegal
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Souleymane Mboup
Laboratory of Bacteriology and Virology, Le Dantec Hospital, Cheikh Anta Diop University, Dakar, Senegal
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Manoj T. Duraisingh
Department of Immunology and Infectious Diseases, Harvard TH Chan School of Public Health, Boston, USA
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  • For correspondence: cbuckee@hsph.harvard.edu mduraisi@hsph.harvard.edu
Caroline O. Buckee
Center for Communicable Disease Dynamics, Department of Epidemiology, Harvard TH Chan School of Public Health, Boston, USA
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  • For correspondence: cbuckee@hsph.harvard.edu mduraisi@hsph.harvard.edu
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Abstract

The growth of the malaria parasite Plasmodium falciparum in human blood causes all clinical manifestations of malaria, a process that begins with the invasion of red blood cells. Parasites enter red blood cells using distinct pairs of parasite ligands and host receptors that define particular invasion pathways. Parasite strains have the capacity to switch between invasion pathways. This flexibility is thought to facilitate immune evasion against particular parasite ligands, but may also reflect the fact that red blood cell surfaces are dynamic and composed of heterogeneous invasion targets. Different host genetic backgrounds affecting red blood cell structure have long been recognized to impact parasite growth in vivo, but even within a host, red blood cells undergo dramatic changes in morphology and receptor density as they age. The consequences of these heterogeneities for parasite growth in vivo remain unclear. Here, we measured the ability of laboratory strains of P. falciparum relying on distinct invasion pathways to enter red blood cells of different ages. We estimated invasion efficiency while accounting for the fact that even if the red blood cells display the appropriate receptors, not all are physically accessible to invading parasites. This approach revealed a tradeoff made by parasites between the fraction of susceptible cells and their invasion rate into them. We were able to distinguish between “specialist” strains exhibiting high invasion rate in fewer cells versus “generalist” strains invading less efficiently into a larger fraction of cells. We developed a mathematical model to predict that infection with a generalist strain would lead to higher peak parasitemias in vivo when compared with a specialist strain with similar overall proliferation rate. Thus, the heterogeneous ecology of red blood cells may play a key role in determining the rate of parasite proliferation between different strains of P. falciparum.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted May 07, 2019.
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Accounting for red blood cell accessibility reveals distinct invasion strategies in Plasmodium falciparum strains
Francisco Cai, Tiffany M. DeSimone, Elsa Hansen, Cameron V. Jennings, Amy K. Bei, Ambroise D. Ahouidi, Souleymane Mboup, Manoj T. Duraisingh, Caroline O. Buckee
bioRxiv 626044; doi: https://doi.org/10.1101/626044
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Accounting for red blood cell accessibility reveals distinct invasion strategies in Plasmodium falciparum strains
Francisco Cai, Tiffany M. DeSimone, Elsa Hansen, Cameron V. Jennings, Amy K. Bei, Ambroise D. Ahouidi, Souleymane Mboup, Manoj T. Duraisingh, Caroline O. Buckee
bioRxiv 626044; doi: https://doi.org/10.1101/626044

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