Transcriptome Analysis of Plasmodium falciparum Isolates From Benin Reveals Specific Gene Expression Associated With Cerebral Malaria

Emilie Guillochon (1, 2) , Jeremy Fraering (2) , Valentin Joste (3, 2) , Claire Kamaliddin (4) , Bertin Vianou (5, 2) , L Houzé (2) , Laura G. Baudrin (6, 7) , Jean-François Faucher (8, 9) , Agnès Aubouy (10) , Sandrine Houzé (3, 2) , Michel Cot (2) , Nicolas Argy (3, 2) , Olivier Taboureau (1) , Gwladys Bertin (2)

1 BFA (UMR_8251 / U1133) - Unité de Biologie Fonctionnelle et Adaptative
2 MERIT - UMR_D 261 - Mère et enfant en milieu tropical : pathogènes, système de santé et transition épidémiologique
3 AP-HP - Hôpital Bichat - Claude Bernard [Paris]
4 University of Calgary
5 IRCB - Institut de Recherche Clinique du Bénin [Abomey-Calavi, Bénin]
6 Institut Curie [Paris]
7 PSL - Université Paris Sciences et Lettres
8 EpiMaCT - Epidémiologie des Maladies Chroniques en zone tropicale
9 Service des Maladies infectieuses et tropicales [CHU Limoges]
10 PHARMA-DEV - Pharmacochimie et Biologie pour le Développement

Cerebral malaria (CM) is the severest form of Plasmodium falciparum infection. Children under 5 years old are those most vulnerable to CM, and they consequently have the highest risk of malaria-related death. Parasite-associated factors leading to CM are not yet fully elucidated. We therefore sought to characterize the gene expression profile associated with CM, using RNA sequencing data from 15 CM and 15 uncomplicated malaria isolates from Benin. Cerebral malaria parasites displayed reduced circulation times, possibly related to higher cytoadherence capacity. Consistent with the latter, we detected increased var genes abundance in CM isolates. Differential expression analyses showed that distinct transcriptome profiles are signatures of malaria severity. Genes involved in adhesion, excluding variant surface antigens, were dysregulated, supporting the idea of increased cytoadhesion capacity of CM parasites. Finally, we found dysregulated expression of genes in the entry into host pathway that may reflect greater erythrocyte invasion capacity of CM parasites.

Mots clés: RNA-seq; cerebral malaria; cytoadherence; transcriptomics; Plasmodium falciparum; var genes

Domaines: Santé publique et épidémiologie

Emilie Guillochon, Jeremy Fraering, Valentin Joste, Claire Kamaliddin, Bertin Vianou, et al.. Transcriptome Analysis of Plasmodium falciparum Isolates From Benin Reveals Specific Gene Expression Associated With Cerebral Malaria. Journal of Infectious Diseases, 2022, 225 (12), ⟨10.1093/infdis/jiac086⟩. ⟨hal-03675332⟩