title: Malaria-infected erythrocyte-derived microvesicles mediate cellular communication within the parasite population and with the host immune system.
abstract: Humans and mice infected with different Plasmodium strains are known to produce microvesicles derived from the infected red blood cells (RBCs), denoted RMVs. Studies in mice have shown that RMVs are elevated during infection and have proinflammatory activity. Here we present a detailed characterization of RMV composition and function in the human malaria parasite Plasmodium falciparum. Proteomics profiling revealed the enrichment of multiple host and parasite proteins, in particular of parasite antigens associated with host cell membranes and proteins involved in parasite invasion into RBCs. RMVs are quantitatively released during the asexual parasite cycle prior to parasite egress. RMVs demonstrate potent immunomodulatory properties on human primary macrophages and neutrophils. Additionally, RMVs are internalized by infected red blood cells and stimulate production of transmission stage parasites in a dose-dependent manner. Thus, RMVs mediate cellular communication within the parasite population and with the host innate immune system.
authors.affiliation: Department of Immunology and Infectious Diseases, Harvard School of Public Health, 665 Huntington Avenue, Boston, MA 02115, USA.
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Mantel
authors.affiliation: BioMEMS Resource Center, Massachusetts General Hospital, 114 16(th) Street, Charlestown, MA 02129, USA.
authors.forename: Anh N
authors.initials: AN
authors.lastname: Hoang
authors.affiliation: Department of Immunology and Infectious Diseases, Harvard School of Public Health, 665 Huntington Avenue, Boston, MA 02115, USA.
authors.forename: Ilana
authors.initials: I
authors.lastname: Goldowitz
authors.affiliation: Program in Cellular and Molecular Medicine, Children's Hospital Boston, 200 Longwood Avenue, Boston, MA 02115, USA; Department of Cell Biology and Histology, Moscow State University, Moscow 119991, Russia.
authors.forename: Daria
authors.initials: D
authors.lastname: Potashnikova
authors.affiliation: BioMEMS Resource Center, Massachusetts General Hospital, 114 16(th) Street, Charlestown, MA 02129, USA.
authors.forename: Bashar
authors.initials: B
authors.lastname: Hamza
authors.affiliation: Program in Cellular and Molecular Medicine, Children's Hospital Boston, 200 Longwood Avenue, Boston, MA 02115, USA; A.N. Belozersky Institute for Physico-Chemical Biology, Moscow State University, Moscow 119991, Russia.
authors.forename: Ivan
authors.initials: I
authors.lastname: Vorobjev
authors.affiliation: Beth Israel Deaconess Medical Center, 3 Blackfan Circle, Boston, MA 02115, USA.
authors.forename: Ionita
authors.initials: I
authors.lastname: Ghiran
authors.affiliation: BioMEMS Resource Center, Massachusetts General Hospital, 114 16(th) Street, Charlestown, MA 02129, USA.
authors.forename: Mehmet
authors.initials: M
authors.lastname: Toner
authors.affiliation: BioMEMS Resource Center, Massachusetts General Hospital, 114 16(th) Street, Charlestown, MA 02129, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Irimia
authors.affiliation: Barnett Institute of Chemical and Biological Analysis, Northeastern University, 360 Huntington Avenue, 412 TF, Boston, MA 02115, USA.
authors.forename: Alexander R
authors.initials: AR
authors.lastname: Ivanov
authors.affiliation: Program in Cellular and Molecular Medicine, Children's Hospital Boston, 200 Longwood Avenue, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA.
authors.forename: Natasha
authors.initials: N
authors.lastname: Barteneva
authors.affiliation: Department of Immunology and Infectious Diseases, Harvard School of Public Health, 665 Huntington Avenue, Boston, MA 02115, USA. Electronic address: mmarti@hsph.harvard.edu.
authors.forename: Matthias
authors.initials: M
authors.lastname: Marti
mesh_terms: D002450:Cell Communication; D055252:Cell-Derived Microparticles / Q000737:chemistry* / Q000378:metabolism*; D004912:Erythrocytes / Q000469:parasitology*; D006790:Host-Parasite Interactions; D006801:Humans; D008264:Macrophages / Q000276:immunology; D009504:Neutrophils / Q000276:immunology; D010963:Plasmodium falciparum / Q000254:growth & development* / Q000276:immunology*; D020543:Proteome / Q000032:analysis; D015398:Signal Transduction
chemical_list: D020543:Proteome