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

Adderley, Jack D. (author)

von Freyend, Simona John (author)

Jackson, Sarah A. (author)

Bird, Megan J. (author)

Burns, Amy L. (author)

Anar, Burcu (author)

Metcalf, Tom (author)

Semblat, Jean-Philippe (author)

Billker, Oliver (author): Umeå universitet,Molekylär Infektionsmedicin, Sverige (MIMS),Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet),Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, UK

Wilson, Danny W. (author)

Doerig, Christian (author)

(creator_code:org_t)

2020-08-11
2020
English.
In: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 11:1

Related links:: https://doi.org/10.1...; show more...; https://umu.diva-por... (primary) (Raw object); https://www.nature.c...; https://urn.kb.se/re...; https://doi.org/10.1...; show less...

Abstract Subject headings

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.

By the author/editor: Adderley, Jack D ...; von Freyend, Sim ...; Jackson, Sarah A ...; Bird, Megan J.; Burns, Amy L.; Anar, Burcu; show more...; Metcalf, Tom; Semblat, Jean-Ph ...; Billker, Oliver; Wilson, Danny W.; Doerig, Christia ...; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Infectious Medic ...

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Immunology in th ...

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