A specific PfEMP1 is expressed in P. falciparum sporozoites and plays a role in hepatocyte infection

TY - JOUR

T1 - A specific PfEMP1 is expressed in P. falciparum sporozoites and plays a role in hepatocyte infection

AU - Zanghì, Gigliola

AU - Vembar, Shruthi S

AU - Baumgarten, Sebastian

AU - Ding, Shuai

AU - Guizetti, Julien

AU - Bryant, Jessica M

AU - Mattei, Denise

AU - Jensen, Anja T R

AU - Rénia, Laurent

AU - Goh, Yun Shan

AU - Sauerwein, Robert

AU - Hermsen, Cornelus C

AU - Franetich, Jean-François

AU - Bordessoulles, Mallaury

AU - Silvie, Olivier

AU - Soulard, Valérie

AU - Scatton, Olivier

AU - Chen, Patty

AU - Mecheri, Salah

AU - Mazier, Dominique

AU - Scherf, Artur

N1 - Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

PY - 2018/3/13

Y1 - 2018/3/13

N2 - 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. P. falciparum PfEMP1 surface adhesion proteins mediate immune evasion and pathogenesis during asexual blood stage development. Zanghì et al. find that a strain-specific member of PfEMP1 is expressed at the sporozoite surface. Antibodies against this protein inhibit sporozoite invasion of hepatocytes in a strain-specific manner.

AB - 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. P. falciparum PfEMP1 surface adhesion proteins mediate immune evasion and pathogenesis during asexual blood stage development. Zanghì et al. find that a strain-specific member of PfEMP1 is expressed at the sporozoite surface. Antibodies against this protein inhibit sporozoite invasion of hepatocytes in a strain-specific manner.

U2 - 10.1016/j.celrep.2018.02.075

DO - 10.1016/j.celrep.2018.02.075

M3 - Journal article

C2 - 29539423

SN - 2211-1247

VL - 22

SP - 2951

EP - 2963

JO - Cell Reports

JF - Cell Reports

IS - 11

ER -