title: A switch in infected erythrocyte deformability at the maturation and blood circulation of Plasmodium falciparum transmission stages.
abstract: Achievement of malaria elimination requires development of novel strategies interfering with parasite transmission, including targeting the parasite sexual stages (gametocytes). The formation of Plasmodium falciparum gametocytes in the human host takes several days during which immature gametocyte-infected erythrocytes (GIEs) sequester in host tissues. Only mature stage GIEs circulate in the peripheral blood, available to uptake by the Anopheles vector. Mechanisms underlying GIE sequestration and release in circulation are virtually unknown. We show here that mature GIEs are more deformable than immature stages using ektacytometry and microsphiltration methods, and that a switch in cellular deformability in the transition from immature to mature gametocytes is accompanied by the deassociation of parasite-derived STEVOR proteins from the infected erythrocyte membrane. We hypothesize that mechanical retention contributes to sequestration of immature GIEs and that regained deformability of mature gametocytes is associated with their release in the bloodstream and ability to circulate. These processes are proposed to play a key role in P falciparum gametocyte development in the host and to represent novel and unconventional targets for interfering with parasite transmission.
authors.affiliation: Dipartimento di Malattie Infettive, Parassitarie e Immunomediate, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Tibúrcio
authors.forename: Makhtar
authors.initials: M
authors.lastname: Niang
authors.forename: Guillaume
authors.initials: G
authors.lastname: Deplaine
authors.forename: Sylvie
authors.initials: S
authors.lastname: Perrot
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Bischoff
authors.forename: Papa Alioune
authors.initials: PA
authors.lastname: Ndour
authors.forename: Francesco
authors.initials: F
authors.lastname: Silvestrini
authors.forename: Ayman
authors.initials: A
authors.lastname: Khattab
authors.forename: Geneviève
authors.initials: G
authors.lastname: Milon
authors.forename: Peter H
authors.initials: PH
authors.lastname: David
authors.forename: Max
authors.initials: M
authors.lastname: Hardeman
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Vernick
authors.forename: Robert W
authors.initials: RW
authors.lastname: Sauerwein
authors.forename: Peter R
authors.initials: PR
authors.lastname: Preiser
authors.forename: Odile
authors.initials: O
authors.lastname: Mercereau-Puijalon
authors.forename: Pierre
authors.initials: P
authors.lastname: Buffet
authors.forename: Pietro
authors.initials: P
authors.lastname: Alano
authors.forename: Catherine
authors.initials: C
authors.lastname: Lavazec
mesh_terms: D000328:Adult; D000818:Animals; D000953:Antigens, Protozoan / Q000378:metabolism; D004907:Erythrocyte Deformability / Q000502:physiology*; D004912:Erythrocytes / Q000469:parasitology*; D005455:Fluorescent Antibody Technique; D006801:Humans; D008018:Life Cycle Stages; D016778:Malaria, Falciparum / Q000097:blood* / Q000469:parasitology / Q000635:transmission*; D010963:Plasmodium falciparum / Q000254:growth & development* / Q000502:physiology* / Q000648:ultrastructure; D021381:Protein Transport
chemical_list: D000953:Antigens, Protozoan; C474556:STEVOR antigen, Plasmodium falciparum