title: Differences in gene transcriptomic pattern of Plasmodium falciparum in children with cerebral malaria and asymptomatic carriers.
abstract: The mechanisms underlying the heterogeneity of clinical malaria remain largely unknown. We hypothesized that differential gene expression contributes to phenotypic variation of parasites which results in a specific interaction with the host, leading to different clinical features of malaria. In this study, we analyzed the transcriptomes of isolates obtained from asymptomatic carriers and patients with uncomplicated or cerebral malaria. We also investigated the transcriptomes of 3D7 clone and 3D7-Lib that expresses severe malaria associated-variant surface antigen. Our findings revealed a specific up-regulation of genes involved in pathogenesis, adhesion to host cell, and erythrocyte aggregation in parasites from patients with cerebral malaria and 3D7-Lib, compared to parasites from asymptomatic carriers and 3D7, respectively. However, we did not find any significant difference between the transcriptomes of parasites from cerebral malaria and uncomplicated malaria, suggesting similar transcriptomic pattern in these two parasite populations. The difference between isolates from asymptomatic children and cerebral malaria concerned genes coding for exported proteins, Maurer's cleft proteins, transcriptional factor proteins, proteins implicated in protein transport, as well as Plasmodium conserved and hypothetical proteins. Interestingly, UPs A1, A2, A3 and UPs B1 of var genes were predominantly found in cerebral malaria-associated isolates and those containing architectural domains of DC4, DC5, DC13 and their neighboring rif genes in 3D7-lib. Therefore, more investigations are needed to analyze the effective role of these genes during malaria infection to provide with new knowledge on malaria pathology. In addition, concomitant regulation of genes within the chromosomal neighborhood suggests a common mechanism of gene regulation in P. falciparum.
authors.affiliation: Institut de Recherche pour le Développement (IRD), UMR 216 Mère et Enfant Face aux Infections Tropicales, Université Paris-Descartes, Près Sorbonne Paris-Cité, Paris, France; PRES Sorbone Paris Cité, Université Paris Descartes, Faculté de Pharmacie, Paris, France.
authors.forename: Talleh
authors.initials: T
authors.lastname: Almelli
authors.affiliation: PRES Sorbone Paris Cité, Université Paris Descartes, Faculté de Pharmacie, Paris, France.
authors.forename: Grégory
authors.initials: G
authors.lastname: Nuel
authors.affiliation: Institut Pasteur, Unit of Molecular Immunology of Parasites, Unit of Insect Vector Genetics and Genomics, Department of Parasitology and Mycology, Paris, France; Centre National de la Recherche Scientifique (CNRS), URA 3012, Paris, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Bischoff
authors.affiliation: Institut de Recherche pour le Développement (IRD), UMR 152 Pharmacochimie et pharmacologie pour le développement - (PHARMA-DEV), Université Paul Sabatier, Toulouse, France.
authors.forename: Agnès
authors.initials: A
authors.lastname: Aubouy
authors.affiliation: Institute of Systems and Synthetic Biology, CNRS, University of Evry, Genopole, Evry, France.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Elati
authors.affiliation: Centre for Medical Parasitology at Department of International Health, Immunology, and Microbiology, University of Copenhagen and at Department of Infectious Diseases, Copenhagen University Hospital (Rigshospitalet), Copenhagen, Denmark.
authors.forename: Christian William
authors.initials: CW
authors.lastname: Wang
authors.affiliation: Plate-forme Transcriptome et Epigénome, Departement Génomes et Génétique, Institut Pasteur, Paris, France.
authors.forename: Marie-Agnès
authors.initials: MA
authors.lastname: Dillies
authors.affiliation: Plate-forme Transcriptome et Epigénome, Departement Génomes et Génétique, Institut Pasteur, Paris, France.
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Coppée
authors.affiliation: Hôpital d'Olembé, Yaoundé, Cameroon.
authors.forename: Georges Nko
authors.initials: GN
authors.lastname: Ayissi
authors.affiliation: Organisation de Coordination pour la lutte contre les Endémies en Afrique Centrale (OCEAC), Laboratoire de Recherche sur le Paludisme, B. P. 288, Yaoundé, Cameroon; Institut de Recherche pour le Développement (IRD), UMR 198 Unité de Recherche des Maladies Infectieuses et Tropicales Emergentes, Faculté de Médecine La Timone, Aix-Marseille Université, Marseille, France.
authors.forename: Leonardo Kishi
authors.initials: LK
authors.lastname: Basco
authors.affiliation: Institut Pasteur de Madagascar, B.P. 1274, Ambatofotsikely, Antananarivo, Madagascar.
authors.forename: Christophe
authors.initials: C
authors.lastname: Rogier
authors.affiliation: Institut de Recherche pour le Développement (IRD), UMR 216 Mère et Enfant Face aux Infections Tropicales, Université Paris-Descartes, Près Sorbonne Paris-Cité, Paris, France; PRES Sorbone Paris Cité, Université Paris Descartes, Faculté de Pharmacie, Paris, France.
authors.forename: Nicaise Tuikue
authors.initials: NT
authors.lastname: Ndam
authors.affiliation: Institut de Recherche pour le Développement (IRD), UMR 216 Mère et Enfant Face aux Infections Tropicales, Université Paris-Descartes, Près Sorbonne Paris-Cité, Paris, France; PRES Sorbone Paris Cité, Université Paris Descartes, Faculté de Pharmacie, Paris, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Deloron
authors.affiliation: Institut de Recherche pour le Développement (IRD), UMR 216 Mère et Enfant Face aux Infections Tropicales, Université Paris-Descartes, Près Sorbonne Paris-Cité, Paris, France; PRES Sorbone Paris Cité, Université Paris Descartes, Faculté de Pharmacie, Paris, France; Organisation de Coordination pour la lutte contre les Endémies en Afrique Centrale (OCEAC), Laboratoire de Recherche sur le Paludisme, B. P. 288, Yaoundé, Cameroon.
authors.forename: Rachida
authors.initials: R
authors.lastname: Tahar
mesh_terms: D002648:Child; D002675:Child, Preschool; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007223:Infant; D016779:Malaria, Cerebral / Q000378:metabolism*; D016778:Malaria, Falciparum / Q000378:metabolism*; D008297:Male; D010963:Plasmodium falciparum / Q000378:metabolism*; D015800:Protozoan Proteins / Q000096:biosynthesis*; D059467:Transcriptome
chemical_list: D015800:Protozoan Proteins