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

Ghania Ramdani; Bernina Naissant; Eloise Thompson; Florence Breil; Audrey Lorthiois; Florian Dupuy; Ross Cummings; Yoann Duffier; Yolanda Corbett; Odile Mercereau-Puijalon; Kenneth Vernick; Donatella Taramelli; David Baker; Gordon Langsley; Catherine Lavazec

doi:10.1371/journal.ppat.1004815

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

Ghania Ramdani ^{1, 2} Bernina Naissant ^{2, 3} Eloise Thompson ⁴ Florence Breil ⁵ Audrey Lorthiois ^{2, 3, 5} Florian Dupuy ^{2, 3} Ross Cummings ⁴ Yoann Duffier ^{2, 3} Yolanda Corbett ⁶ Odile Mercereau-Puijalon ⁷ Kenneth Vernick ⁸ Donatella Taramelli ⁶ David Baker ⁴ Gordon Langsley ^{1, 2, *} Catherine Lavazec ^{2, 3, 8, *}

* Auteur correspondant

1 Laboratoire de Biologie Cellulaire Comparative des Apicomplexes

2 UM3 (UMR 8104 / U1016) - Institut Cochin

3 Laboratoire de Biologie de la Transmission de Plasmodium

4 Faculty of Infectious and Tropical Diseases

5 Génétique et Génomique des Insectes vecteurs

6 DiSFeB - Dipartimento di Scienze Farmacologiche e Biomolecolari

7 Immunologie moléculaire des parasites

8 Génétique et Génomique des Insectes Vecteurs

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〉

Domaine :

Sciences du Vivant [q-bio] / Biochimie, Biologie Moléculaire

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

journal.ppat.1004815.pdf

Fichiers éditeurs autorisés sur une archive ouverte

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

Fichier

Identifiants

Collections

Citation

Exporter

Métriques

335

175

Contact

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

Fichier

Identifiants

Collections

Citation

Exporter

Partager

Métriques

335

175

Contact