Erythrocyte phospho-signalling is dynamically altered during infection with Plasmodium falciparum

It is well established that intracellular pathogens mobilise signalling pathways to manipulate gene expression of their host cell to promote their own survival. Surprisingly, there is evidence that specific host signalling molecules are likewise activated in a-nucleated erythrocytes in response to i...

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Main Authors: Jack D. Adderley, Christian Doerig
Format: Article
Language:English
Published: Shared Science Publishers OG 2020-09-01
Series:Microbial Cell
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Online Access:http://microbialcell.com/researcharticles/2020a-adderley-microbial-cell/
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author Jack D. Adderley
Christian Doerig
author_facet Jack D. Adderley
Christian Doerig
author_sort Jack D. Adderley
collection DOAJ
description It is well established that intracellular pathogens mobilise signalling pathways to manipulate gene expression of their host cell to promote their own survival. Surprisingly, there is evidence that specific host signalling molecules are likewise activated in a-nucleated erythrocytes in response to infection with malaria parasites. In this paper (Adderley et al., Nature Communications 2020), we report the system-wide assessment of host erythrocyte signalling during the course of infection with Plasmodium falciparum. This was achieved through the use of antibody microarrays containing >800 antibodies directed against human signalling proteins, which enabled us to interrogate the status of host erythrocyte signalling pathways at the ring, trophozoite and schizont stages of parasite development. This not only confirmed the pre-existing fragmentary data on the activation of a host erythrocyte PAK-MEK pathway, but also identified dynamic changes to many additional signalling elements, with trophozoite-infected erythrocytes displaying the largest mobilisation of host cell signalling. This study generated a comprehensive dataset on the modulation of host erythrocyte signalling during infection with P. falciparum, and provides the proof of principle that human protein kinases activated by Plasmodium infection represent attractive targets for antimalarial intervention.
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spelling doaj-art-02a8b3f082b44dc58f0aee7dec81c7db2025-08-20T02:05:21ZengShared Science Publishers OGMicrobial Cell2311-26382020-09-0171028628810.15698/mic2020.10.733Erythrocyte phospho-signalling is dynamically altered during infection with Plasmodium falciparumJack D. Adderley0Christian Doerig1Centre for Chronic Infectious and Inflammation Disease, Biomedical Sciences Cluster, School of Health and Biomedical Sciences, RMIT University, Bundoora VIC 3083, Australia.Centre for Chronic Infectious and Inflammation Disease, Biomedical Sciences Cluster, School of Health and Biomedical Sciences, RMIT University, Bundoora VIC 3083, Australia.It is well established that intracellular pathogens mobilise signalling pathways to manipulate gene expression of their host cell to promote their own survival. Surprisingly, there is evidence that specific host signalling molecules are likewise activated in a-nucleated erythrocytes in response to infection with malaria parasites. In this paper (Adderley et al., Nature Communications 2020), we report the system-wide assessment of host erythrocyte signalling during the course of infection with Plasmodium falciparum. This was achieved through the use of antibody microarrays containing >800 antibodies directed against human signalling proteins, which enabled us to interrogate the status of host erythrocyte signalling pathways at the ring, trophozoite and schizont stages of parasite development. This not only confirmed the pre-existing fragmentary data on the activation of a host erythrocyte PAK-MEK pathway, but also identified dynamic changes to many additional signalling elements, with trophozoite-infected erythrocytes displaying the largest mobilisation of host cell signalling. This study generated a comprehensive dataset on the modulation of host erythrocyte signalling during infection with P. falciparum, and provides the proof of principle that human protein kinases activated by Plasmodium infection represent attractive targets for antimalarial intervention.http://microbialcell.com/researcharticles/2020a-adderley-microbial-cell/malariaprotein kinasekinomicshost-directed therapy hdthost-pathogen interactionssignaling
spellingShingle Jack D. Adderley
Christian Doerig
Erythrocyte phospho-signalling is dynamically altered during infection with Plasmodium falciparum
Microbial Cell
malaria
protein kinase
kinomics
host-directed therapy hdt
host-pathogen interactions
signaling
title Erythrocyte phospho-signalling is dynamically altered during infection with Plasmodium falciparum
title_full Erythrocyte phospho-signalling is dynamically altered during infection with Plasmodium falciparum
title_fullStr Erythrocyte phospho-signalling is dynamically altered during infection with Plasmodium falciparum
title_full_unstemmed Erythrocyte phospho-signalling is dynamically altered during infection with Plasmodium falciparum
title_short Erythrocyte phospho-signalling is dynamically altered during infection with Plasmodium falciparum
title_sort erythrocyte phospho signalling is dynamically altered during infection with plasmodium falciparum
topic malaria
protein kinase
kinomics
host-directed therapy hdt
host-pathogen interactions
signaling
url http://microbialcell.com/researcharticles/2020a-adderley-microbial-cell/
work_keys_str_mv AT jackdadderley erythrocytephosphosignallingisdynamicallyalteredduringinfectionwithplasmodiumfalciparum
AT christiandoerig erythrocytephosphosignallingisdynamicallyalteredduringinfectionwithplasmodiumfalciparum