Transcriptional profiling of hepatocytes infected with the replicative form of the malaria parasite Plasmodium cynomolgi

Abstract Background The zoonotic simian parasite Plasmodium cynomolgi develops into replicating schizonts and dormant hypnozoites during the infection of hepatocytes and is used as a model organism to study relapsing malaria. The transcriptional profiling of P. cynomolgi liver stages was previously...

Full description

Bibliographic Details
Main Authors: Gabriel Mitchell, Guglielmo Roma, Annemarie Voorberg-van der Wel, Martin Beibel, Anne-Marie Zeeman, Sven Schuierer, Laura Torres, Erika L. Flannery, Clemens H. M. Kocken, Sebastian A. Mikolajczak, Thierry T. Diagana
Format: Article
Language:English
Published: BMC 2022-12-01
Series:Malaria Journal
Subjects:
Online Access:https://doi.org/10.1186/s12936-022-04411-3
_version_ 1797977582303444992
author Gabriel Mitchell
Guglielmo Roma
Annemarie Voorberg-van der Wel
Martin Beibel
Anne-Marie Zeeman
Sven Schuierer
Laura Torres
Erika L. Flannery
Clemens H. M. Kocken
Sebastian A. Mikolajczak
Thierry T. Diagana
author_facet Gabriel Mitchell
Guglielmo Roma
Annemarie Voorberg-van der Wel
Martin Beibel
Anne-Marie Zeeman
Sven Schuierer
Laura Torres
Erika L. Flannery
Clemens H. M. Kocken
Sebastian A. Mikolajczak
Thierry T. Diagana
author_sort Gabriel Mitchell
collection DOAJ
description Abstract Background The zoonotic simian parasite Plasmodium cynomolgi develops into replicating schizonts and dormant hypnozoites during the infection of hepatocytes and is used as a model organism to study relapsing malaria. The transcriptional profiling of P. cynomolgi liver stages was previously reported and revealed many important biological features of the parasite but left out the host response to malaria infection. Methods Previously published RNA sequencing data were used to quantify the expression of host genes in rhesus macaque hepatocytes infected with P . cynomolgi in comparison to either cells from uninfected samples or uninfected bystander cells. Results Although the dataset could not be used to resolve the transcriptional profile of hypnozoite-infected hepatocytes, it provided a snapshot of the host response to liver stage schizonts at 9–10 day post-infection and identified specific host pathways that are modulated during the exo-erythrocytic stage of P. cynomolgi. Conclusions This study constitutes a valuable resource characterizing the hepatocyte response to P. cynomolgi infection and provides a framework to build on future research that aims at understanding hepatocyte-parasite interactions during relapsing malaria infection.
first_indexed 2024-04-11T05:09:18Z
format Article
id doaj.art-0e680a8fe8ac407888ecdc3feea9dfd8
institution Directory Open Access Journal
issn 1475-2875
language English
last_indexed 2024-04-11T05:09:18Z
publishDate 2022-12-01
publisher BMC
record_format Article
series Malaria Journal
spelling doaj.art-0e680a8fe8ac407888ecdc3feea9dfd82022-12-25T12:06:00ZengBMCMalaria Journal1475-28752022-12-0121111210.1186/s12936-022-04411-3Transcriptional profiling of hepatocytes infected with the replicative form of the malaria parasite Plasmodium cynomolgiGabriel Mitchell0Guglielmo Roma1Annemarie Voorberg-van der Wel2Martin Beibel3Anne-Marie Zeeman4Sven Schuierer5Laura Torres6Erika L. Flannery7Clemens H. M. Kocken8Sebastian A. Mikolajczak9Thierry T. Diagana10Open Innovation at Novartis Institute for Tropical Diseases, Novartis Institutes for BioMedical ResearchChemical Biology & Therapeutics, Novartis Institutes for BioMedical ResearchDepartment of Parasitology, Biomedical Primate Research CentreChemical Biology & Therapeutics, Novartis Institutes for BioMedical ResearchDepartment of Parasitology, Biomedical Primate Research CentreChemical Biology & Therapeutics, Novartis Institutes for BioMedical ResearchOpen Innovation at Novartis Institute for Tropical Diseases, Novartis Institutes for BioMedical ResearchNovartis Institute for Tropical Diseases, Novartis Institutes for BioMedical ResearchDepartment of Parasitology, Biomedical Primate Research CentreNovartis Institute for Tropical Diseases, Novartis Institutes for BioMedical ResearchNovartis Institute for Tropical Diseases, Novartis Institutes for BioMedical ResearchAbstract Background The zoonotic simian parasite Plasmodium cynomolgi develops into replicating schizonts and dormant hypnozoites during the infection of hepatocytes and is used as a model organism to study relapsing malaria. The transcriptional profiling of P. cynomolgi liver stages was previously reported and revealed many important biological features of the parasite but left out the host response to malaria infection. Methods Previously published RNA sequencing data were used to quantify the expression of host genes in rhesus macaque hepatocytes infected with P . cynomolgi in comparison to either cells from uninfected samples or uninfected bystander cells. Results Although the dataset could not be used to resolve the transcriptional profile of hypnozoite-infected hepatocytes, it provided a snapshot of the host response to liver stage schizonts at 9–10 day post-infection and identified specific host pathways that are modulated during the exo-erythrocytic stage of P. cynomolgi. Conclusions This study constitutes a valuable resource characterizing the hepatocyte response to P. cynomolgi infection and provides a framework to build on future research that aims at understanding hepatocyte-parasite interactions during relapsing malaria infection.https://doi.org/10.1186/s12936-022-04411-3Host responseRelapsing malariaSchizontsHypnozoitesRNA sequencingLiver cells
spellingShingle Gabriel Mitchell
Guglielmo Roma
Annemarie Voorberg-van der Wel
Martin Beibel
Anne-Marie Zeeman
Sven Schuierer
Laura Torres
Erika L. Flannery
Clemens H. M. Kocken
Sebastian A. Mikolajczak
Thierry T. Diagana
Transcriptional profiling of hepatocytes infected with the replicative form of the malaria parasite Plasmodium cynomolgi
Malaria Journal
Host response
Relapsing malaria
Schizonts
Hypnozoites
RNA sequencing
Liver cells
title Transcriptional profiling of hepatocytes infected with the replicative form of the malaria parasite Plasmodium cynomolgi
title_full Transcriptional profiling of hepatocytes infected with the replicative form of the malaria parasite Plasmodium cynomolgi
title_fullStr Transcriptional profiling of hepatocytes infected with the replicative form of the malaria parasite Plasmodium cynomolgi
title_full_unstemmed Transcriptional profiling of hepatocytes infected with the replicative form of the malaria parasite Plasmodium cynomolgi
title_short Transcriptional profiling of hepatocytes infected with the replicative form of the malaria parasite Plasmodium cynomolgi
title_sort transcriptional profiling of hepatocytes infected with the replicative form of the malaria parasite plasmodium cynomolgi
topic Host response
Relapsing malaria
Schizonts
Hypnozoites
RNA sequencing
Liver cells
url https://doi.org/10.1186/s12936-022-04411-3
work_keys_str_mv AT gabrielmitchell transcriptionalprofilingofhepatocytesinfectedwiththereplicativeformofthemalariaparasiteplasmodiumcynomolgi
AT guglielmoroma transcriptionalprofilingofhepatocytesinfectedwiththereplicativeformofthemalariaparasiteplasmodiumcynomolgi
AT annemarievoorbergvanderwel transcriptionalprofilingofhepatocytesinfectedwiththereplicativeformofthemalariaparasiteplasmodiumcynomolgi
AT martinbeibel transcriptionalprofilingofhepatocytesinfectedwiththereplicativeformofthemalariaparasiteplasmodiumcynomolgi
AT annemariezeeman transcriptionalprofilingofhepatocytesinfectedwiththereplicativeformofthemalariaparasiteplasmodiumcynomolgi
AT svenschuierer transcriptionalprofilingofhepatocytesinfectedwiththereplicativeformofthemalariaparasiteplasmodiumcynomolgi
AT lauratorres transcriptionalprofilingofhepatocytesinfectedwiththereplicativeformofthemalariaparasiteplasmodiumcynomolgi
AT erikalflannery transcriptionalprofilingofhepatocytesinfectedwiththereplicativeformofthemalariaparasiteplasmodiumcynomolgi
AT clemenshmkocken transcriptionalprofilingofhepatocytesinfectedwiththereplicativeformofthemalariaparasiteplasmodiumcynomolgi
AT sebastianamikolajczak transcriptionalprofilingofhepatocytesinfectedwiththereplicativeformofthemalariaparasiteplasmodiumcynomolgi
AT thierrytdiagana transcriptionalprofilingofhepatocytesinfectedwiththereplicativeformofthemalariaparasiteplasmodiumcynomolgi