Article open access publication

A Specific PfEMP1 Is Expressed in P. falciparum Sporozoites and Plays a Role in Hepatocyte Infection

Cell Reports, Elsevier, ISSN 2211-1247

Volume 22, 11, 2018

DOI:10.1016/j.celrep.2018.02.075, Dimensions: pub.1101513015, PMC: PMC5863040, PMID: 29539423,

Authors

Zanghi, Gigliola (1) (2) (3) (4) (5) (6)
Vembar, Shruthi S. (4) (5) (6)
Baumgarten, Sebastian (4) (5) (6)
Ding, Shuai (4) (5) (6)
Guizetti, Julien (4) (5) (6)
Bryant, Jessica M (4) (5) (6)
Mattei, Denise (4) (5) (6)
Rénia, Laurent (9) (10)
Silvie, Olivier (1) (2) (3)
Soulard, Valerie (1) (2) (3)
Chen, Patty (4) (5) (6)
Mecheri, Salah (4) (5) (6)
Mazier, Dominique * (1) (2) (3)
Scherf, Artur * (4) (5) (6)

* Corresponding author

Affiliations

Organisations

  1. (1) Pitié-Salpêtrière Hospital, grid.411439.a
  2. (2) Délégation Paris 11, grid.457369.a
  3. (3) Sorbonne University, grid.462844.8
  4. (4) French Institute of Health and Medical Research, grid.7429.8
  5. (5) French National Centre for Scientific Research, grid.4444.0
  6. (6) Institut Pasteur, grid.428999.7
  7. (7) Department of Infectious Diseases, Copenhagen University Hospital (Rigshospitalet), 2100 Copenhagen, Denmark
  8. (8) University of Copenhagen, grid.5254.6, KU
  9. (9) National University of Singapore, grid.4280.e
  10. (10) Singapore Immunology Network, grid.430276.4
  11. (11) Radboud University Nijmegen Medical Centre, grid.10417.33

Description

Heterochromatin plays a central role in the process of immune evasion, pathogenesis, and transmission of the malaria parasite Plasmodium falciparum during blood stage infection. Here, we use ChIP sequencing to demonstrate that sporozoites from mosquito salivary glands expand heterochromatin at subtelomeric regions to silence blood-stage-specific genes. Our data also revealed that heterochromatin enrichment is predictive of the transcription status of clonally variant genes members that mediate cytoadhesion in blood stage parasites. A specific member (here called NF54varsporo) of the var gene family remains euchromatic, and the resultant PfEMP1 (NF54_SpzPfEMP1) is expressed at the sporozoite surface. NF54_SpzPfEMP1-specific antibodies efficiently block hepatocyte infection in a strain-specific manner. Furthermore, human volunteers immunized with infective sporozoites developed antibodies against NF54_SpzPfEMP1. Overall, we show that the epigenetic signature of var genes is reset in mosquito stages. Moreover, the identification of a strain-specific sporozoite PfEMP1 is highly relevant for vaccine design based on sporozoites.

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Research area: Medicine

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Research area: Medicine

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Times Cited: 29

Field Citation Ratio (FCR): 10.31

Relative Citation ratio (RCR): 2.89

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