Format

Send to

Choose Destination
Cell Rep. 2018 Mar 13;22(11):2951-2963. doi: 10.1016/j.celrep.2018.02.075.

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

Author information

1
Sorbonne Universités, Université Pierre et Marie Curie-Paris 6, UMR S945, 75003 Paris, France; Institut National de la Santé et de la Recherche Médicale, U945, 75013 Paris, France; Unité Biologie des Interactions Hôte-Parasite, Département de Parasites et Insectes Vecteurs, Institut Pasteur, 75015 Paris, France; CNRS, ERL 9195, 75015 Paris, France; INSERM, Unit U1201, 75015 Paris, France; AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Service de Parasitologie Mycologie, Paris 75013, France.
2
Unité Biologie des Interactions Hôte-Parasite, Département de Parasites et Insectes Vecteurs, Institut Pasteur, 75015 Paris, France; CNRS, ERL 9195, 75015 Paris, France; INSERM, Unit U1201, 75015 Paris, France.
3
Centre for Medical Parasitology, Department of Immunology & Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Infectious Diseases, Copenhagen University Hospital (Rigshospitalet), 2100 Copenhagen, Denmark.
4
Laboratory of Pathogen Immunobiology, Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A(∗)STAR), Biopolis, Singapore; Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
5
Laboratory of Pathogen Immunobiology, Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A(∗)STAR), Biopolis, Singapore.
6
Department of Medical Microbiology and Radboud Center for Infectious Diseases, Radboud University Medical Center, P.O. Box 9101, 6500 HB, Nijmegen, the Netherlands.
7
Sorbonne Universités, Université Pierre et Marie Curie-Paris 6, UMR S945, 75003 Paris, France; Institut National de la Santé et de la Recherche Médicale, U945, 75013 Paris, France; AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Service de Parasitologie Mycologie, Paris 75013, France.
8
Service de Chirurgie Digestive, Hépato-Bilio-Pancréatique et Transplantation Hépatique, Hôpital Pitié-Salpêtrière, 75013 Paris, France.
9
Sorbonne Universités, Université Pierre et Marie Curie-Paris 6, UMR S945, 75003 Paris, France; Institut National de la Santé et de la Recherche Médicale, U945, 75013 Paris, France; AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Service de Parasitologie Mycologie, Paris 75013, France. Electronic address: dominique.mazier@upmc.fr.
10
Unité Biologie des Interactions Hôte-Parasite, Département de Parasites et Insectes Vecteurs, Institut Pasteur, 75015 Paris, France; CNRS, ERL 9195, 75015 Paris, France; INSERM, Unit U1201, 75015 Paris, France. Electronic address: artur.scherf@pasteur.fr.

Abstract

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.

KEYWORDS:

P. falciparum; PfEMP1; PfHP1; epigenetic; hepatocyte infection; heterochromatin; malaria; sporozoite; var genes

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center