Early gametocytes of the malaria parasite Plasmodium falciparum specifically remodel the adhesive properties of infected erythrocyte surface

Authors

  • Marta Tibúrcio,

    1. Dipartimento di Malattie Infettive, Parassitarie ed Immunomediate, Istituto Superiore di Sanità, Rome, Italy
    Search for more papers by this author
  • Francesco Silvestrini,

    1. Dipartimento di Malattie Infettive, Parassitarie ed Immunomediate, Istituto Superiore di Sanità, Rome, Italy
    Search for more papers by this author
  • Lucia Bertuccini,

    1. Dipartimento di Tecnologie e Salute, Istituto Superiore di Sanità, Rome, Italy
    Search for more papers by this author
  • Adam Frederik Sander,

    1. Department of International Health, Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark
    2. Department of Infectious Diseases, Copenhagen University Hospital, Copenhagen, Denmark
    Search for more papers by this author
  • Louise Turner,

    1. Department of International Health, Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark
    2. Department of Infectious Diseases, Copenhagen University Hospital, Copenhagen, Denmark
    Search for more papers by this author
  • Thomas Lavstsen,

    1. Department of International Health, Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark
    2. Department of Infectious Diseases, Copenhagen University Hospital, Copenhagen, Denmark
    Search for more papers by this author
  • Pietro Alano

    Corresponding author
    • Dipartimento di Malattie Infettive, Parassitarie ed Immunomediate, Istituto Superiore di Sanità, Rome, Italy
    Search for more papers by this author

For correspondence. E-mail alano@iss.it; Tel. (+39) 0649902868; Fax (+39) 0649902226.

Summary

In Plasmodium falciparum infections the parasite transmission stages, the gametocytes, mature in 10 days sequestered in internal organs. Recent studies suggest that cell mechanical properties rather than adhesive interactions play a role in sequestration during gametocyte maturation. It remains instead obscure how sequestration is established, and how the earliest sexual stages, morphologically similar to asexual trophozoites, modify the infected erythrocytes and their cytoadhesive properties at the onset of gametocytogenesis. Here, purified P. falciparum early gametocytes were used to ultrastructurally and biochemically analyse parasite-induced modifications on the red blood cell surface and to measure their functional consequences on adhesion to human endothelial cells. This work revealed that stage I gametocytes are able to deform the infected erythrocytes like asexual parasites, but do not modify its surface with adhesive ‘knob’ structures and associated proteins. Reduced levels of the P. falciparum erythrocyte membrane protein 1 (PfEMP1) adhesins are exposed on the red blood cell surface bythese parasites, and the expression of the var gene family, which encodes 50–60 variants of PfEMP1, is dramatically downregulated in the transition from asexual development to gametocytogenesis. Cytoadhesion assays show that such gene expression changes and host cell surface modifications functionally result in the inability of stage I gametocytes to bind the host ligands used by the asexual parasite to bind endothelial cells. In conclusion, these results identify specific differences in molecular and cellular mechanisms of host cell remodelling and in adhesive properties, leading to clearly distinct host parasite interplays in the establishment of sequestration of stage I gametocytes and of asexual trophozoites.

Ancillary