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|Title:||Analysis of erythrocyte signalling pathways during Plasmodium falciparum infection identifies targets for host-directed antimalarial intervention|
John von Freyend, S.
|Citation:||Nature Communications, 2020; 11(1):4015|
|Jack D. Adderley, Simona John von Freyend, Sarah A. Jackson, Megan J. Bird, Amy L. Burns ... Danny Wilson ... et al.|
|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.|
|Keywords:||Erythrocytes; Humans; Plasmodium falciparum; Malaria, Falciparum; Proto-Oncogene Proteins B-raf; Protein Kinase Inhibitors; Antimalarials; Protein Array Analysis; Inhibitory Concentration 50; Signal Transduction; Phosphorylation; Life Cycle Stages; Proto-Oncogene Proteins c-met; Host-Parasite Interactions|
|Rights:||© The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/ licenses/by/4.0/.|
|Appears in Collections:||Environment Institute publications|
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