Analysis of erythrocyte signalling pathways during Plasmodium falciparum infection identifies targets for host-directed antimalarial intervention

Jack D. Adderley, Simona John von Freyend, Sarah A. Jackson, Megan J. Bird, Amy L. Burns, Burcu Anar, Tom Metcalf, Jean-Philippe Semblat, Oliver Billker, Danny W. Wilson and Christian Doerig ()
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Jack D. Adderley: RMIT University
Simona John von Freyend: Monash University
Sarah A. Jackson: Monash University
Megan J. Bird: Monash University
Amy L. Burns: University of Adelaide
Burcu Anar: Wellcome Trust Sanger Institute
Tom Metcalf: Wellcome Trust Sanger Institute
Jean-Philippe Semblat: Institut National de la Transfusion Sanguine, Inserm UMR S1134
Oliver Billker: Wellcome Trust Sanger Institute
Danny W. Wilson: University of Adelaide
Christian Doerig: RMIT University

Nature Communications, 2020, vol. 11, issue 1, 1-13

Abstract: Abstract Intracellular pathogens mobilize host signaling pathways of their host cell to promote their own survival. Evidence is emerging that signal transduction elements are activated in a-nucleated erythrocytes in response to infection with malaria parasites, but the extent of this phenomenon remains unknown. Here, we fill this knowledge gap through a comprehensive and dynamic assessment of host erythrocyte signaling during infection with Plasmodium falciparum. We used arrays of 878 antibodies directed against human signaling proteins to interrogate the activation status of host erythrocyte phospho-signaling pathways at three blood stages of parasite asexual development. This analysis reveals a dynamic modulation of many host signalling proteins across parasite development. Here we focus on the hepatocyte growth factor receptor (c-MET) and the MAP kinase pathway component B-Raf, providing a proof of concept that human signaling kinases identified as activated by malaria infection represent attractive targets for antimalarial intervention.

Date: 2020
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DOI: 10.1038/s41467-020-17829-7

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