title: Pf155/RESA protein influences the dynamic microcirculatory behavior of ring-stage Plasmodium falciparum infected red blood cells.
abstract: Proteins exported by Plasmodium falciparum to the red blood cell (RBC) membrane modify the structural properties of the parasitized RBC (Pf-RBC). Although quasi-static single cell assays show reduced ring-stage Pf-RBCs deformability, the parameters influencing their microcirculatory behavior remain unexplored. Here, we study the dynamic properties of ring-stage Pf-RBCs and the role of the parasite protein Pf155/Ring-Infected Erythrocyte Surface Antigen (RESA). Diffraction phase microscopy revealed RESA-driven decreased Pf-RBCs membrane fluctuations. Microfluidic experiments showed a RESA-dependent reduction in the Pf-RBCs transit velocity, which was potentiated at febrile temperature. In a microspheres filtration system, incubation at febrile temperature impaired traversal of RESA-expressing Pf-RBCs. These results show that RESA influences ring-stage Pf-RBCs microcirculation, an effect that is fever-enhanced. This is the first identification of a parasite factor influencing the dynamic circulation of young asexual Pf-RBCs in physiologically relevant conditions, offering novel possibilities for interventions to reduce parasite survival and pathogenesis in its human host.
authors.affiliation: Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. mdiez@mit.edu
authors.forename: Monica
authors.initials: M
authors.lastname: Diez-Silva
authors.forename: YongKeun
authors.initials: Y
authors.lastname: Park
authors.forename: Sha
authors.initials: S
authors.lastname: Huang
authors.forename: Hansen
authors.initials: H
authors.lastname: Bow
authors.forename: Odile
authors.initials: O
authors.lastname: Mercereau-Puijalon
authors.forename: Guillaume
authors.initials: G
authors.lastname: Deplaine
authors.forename: Catherine
authors.initials: C
authors.lastname: Lavazec
authors.forename: Sylvie
authors.initials: S
authors.lastname: Perrot
authors.forename: Serge
authors.initials: S
authors.lastname: Bonnefoy
authors.forename: Michael S
authors.initials: MS
authors.lastname: Feld
authors.forename: Jongyoon
authors.initials: J
authors.lastname: Han
authors.forename: Ming
authors.initials: M
authors.lastname: Dao
authors.forename: Subra
authors.initials: S
authors.lastname: Suresh
mesh_terms: D002462:Cell Membrane / Q000378:metabolism; D004912:Erythrocytes / Q000378:metabolism* / Q000469:parasitology*; D006801:Humans; D010963:Plasmodium falciparum / Q000254:growth & development / Q000378:metabolism*; D015800:Protozoan Proteins / Q000378:metabolism*; D013696:Temperature
chemical_list: D015800:Protozoan Proteins; C050256:ring-infected erythrocyte surface antigen (RESA), Plasmodium falciparum