Neutrophils impose strong immune pressure against PfEMP1 variants implicated in cerebral malaria
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Neutrophils impose strong immune pressure against PfEMP1 variants implicated in cerebral malaria. / Zelter, Tamir; Strahilevitz, Jacob; Simantov, Karina; Yajuk, Olga; Adams, Yvonne; Ramstedt Jensen, Anja; Dzikowski, Ron; Granot, Zvi.
In: EMBO Reports, Vol. 23, e53641, 2022.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Neutrophils impose strong immune pressure against PfEMP1 variants implicated in cerebral malaria
AU - Zelter, Tamir
AU - Strahilevitz, Jacob
AU - Simantov, Karina
AU - Yajuk, Olga
AU - Adams, Yvonne
AU - Ramstedt Jensen, Anja
AU - Dzikowski, Ron
AU - Granot, Zvi
N1 - Publisher Copyright: © 2022 The Authors. Published under the terms of the CC BY NC ND 4.0 license.
PY - 2022
Y1 - 2022
N2 - Plasmodium falciparum, the deadliest form of human malaria, remains one of the major threats to human health in endemic regions. Its virulence is attributed to its ability to modify infected red blood cells (iRBC) to adhere to endothelial receptors by placing variable antigens known as PfEMP1 on the iRBC surface. PfEMP1 expression determines the cytoadhesive properties of the iRBCs and is implicated in severe malaria. To evade antibody-mediated responses, the parasite undergoes continuous switches of expression between different PfEMP1 variants. Recently, it became clear that in addition to antibody-mediated responses, PfEMP1 triggers innate immune responses; however, the role of neutrophils, the most abundant white blood cells in the human circulation, in malaria remains elusive. Here, we show that neutrophils recognize and kill blood-stage P. falciparum isolates. We identify neutrophil ICAM-1 and specific PfEMP1 implicated in cerebral malaria as the key molecules involved in this killing. Our data provide mechanistic insight into the interactions between neutrophils and iRBCs and demonstrate the important influence of PfEMP1 on the selective innate response to cerebral malaria.
AB - Plasmodium falciparum, the deadliest form of human malaria, remains one of the major threats to human health in endemic regions. Its virulence is attributed to its ability to modify infected red blood cells (iRBC) to adhere to endothelial receptors by placing variable antigens known as PfEMP1 on the iRBC surface. PfEMP1 expression determines the cytoadhesive properties of the iRBCs and is implicated in severe malaria. To evade antibody-mediated responses, the parasite undergoes continuous switches of expression between different PfEMP1 variants. Recently, it became clear that in addition to antibody-mediated responses, PfEMP1 triggers innate immune responses; however, the role of neutrophils, the most abundant white blood cells in the human circulation, in malaria remains elusive. Here, we show that neutrophils recognize and kill blood-stage P. falciparum isolates. We identify neutrophil ICAM-1 and specific PfEMP1 implicated in cerebral malaria as the key molecules involved in this killing. Our data provide mechanistic insight into the interactions between neutrophils and iRBCs and demonstrate the important influence of PfEMP1 on the selective innate response to cerebral malaria.
KW - cerebral malaria
KW - ICAM1
KW - neutrophils
KW - PfEMP1
KW - Plasmodium falciparum
U2 - 10.15252/embr.202153641
DO - 10.15252/embr.202153641
M3 - Journal article
C2 - 35417070
AN - SCOPUS:85128165655
VL - 23
JO - E M B O Reports
JF - E M B O Reports
SN - 1469-221X
M1 - e53641
ER -
ID: 305716440