Skip to Main content Skip to Navigation
Journal articles

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.
Document type :
Journal articles
Complete list of metadata

Cited literature [58 references]  Display  Hide  Download
Contributor : Mireille Bos Connect in order to contact the contributor
Submitted on : Tuesday, May 19, 2015 - 4:31:37 PM
Last modification on : Thursday, April 7, 2022 - 10:10:30 AM
Long-term archiving on: : Thursday, April 20, 2017 - 3:39:19 AM


Publisher files allowed on an open archive



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⟩



Record views


Files downloads