cAMP-Signalling Regulates Gametocyte-Infected Erythrocyte Deformability Required for Malaria Parasite Transmission.

Abstract : Blocking Plasmodium falciparum transmission to mosquitoes has been designated a strategic objective in the global agenda of malaria elimination. Transmission is ensured by gametocyte-infected erythrocytes (GIE) that sequester in the bone marrow and at maturation are released into peripheral blood from where they are taken up during a mosquito blood meal. Release into the blood circulation is accompanied by an increase in GIE deformability that allows them to pass through the spleen. Here, we used a microsphere matrix to mimic splenic filtration and investigated the role of cAMP-signalling in regulating GIE deformability. We demonstrated that mature GIE deformability is dependent on reduced cAMP-signalling and on increased phosphodiesterase expression in stage V gametocytes, and that parasite cAMP-dependent kinase activity contributes to the stiffness of immature gametocytes. Importantly, pharmacological agents that raise cAMP levels in transmissible stage V gametocytes render them less deformable and hence less likely to circulate through the spleen. Therefore, phosphodiesterase inhibitors that raise cAMP levels in P. falciparum infected erythrocytes, such as sildenafil, represent new candidate drugs to block transmission of malaria parasites.
Type de document :
Article dans une revue
PLoS Pathogens, Public Library of Science, 2015, 11 (5), pp.e1004815. 〈10.1371/journal.ppat.1004815〉
Liste complète des métadonnées

Littérature citée [58 références]  Voir  Masquer  Télécharger

http://www.hal.inserm.fr/inserm-01153365
Contributeur : Mireille Bos <>
Soumis le : mardi 19 mai 2015 - 16:31:37
Dernière modification le : jeudi 11 janvier 2018 - 06:28:08
Document(s) archivé(s) le : jeudi 20 avril 2017 - 03:39:19

Fichier

journal.ppat.1004815.pdf
Fichiers éditeurs autorisés sur une archive ouverte

Identifiants

Collections

Citation

Ghania Ramdani, Bernina Naissant, Eloise Thompson, Florence Breil, Audrey Lorthiois, et al.. cAMP-Signalling Regulates Gametocyte-Infected Erythrocyte Deformability Required for Malaria Parasite Transmission.. PLoS Pathogens, Public Library of Science, 2015, 11 (5), pp.e1004815. 〈10.1371/journal.ppat.1004815〉. 〈inserm-01153365〉

Partager

Métriques

Consultations de la notice

335

Téléchargements de fichiers

175