Plasmodium P36 determines host cell receptor usage during sporozoite invasion

ELife
Giulia ManzoniOlivier Silvie

Abstract

Plasmodium sporozoites, the mosquito-transmitted forms of the malaria parasite, first infect the liver for an initial round of replication before the emergence of pathogenic blood stages. Sporozoites represent attractive targets for antimalarial preventive strategies, yet the mechanisms of parasite entry into hepatocytes remain poorly understood. Here we show that the two main species causing malaria in humans, Plasmodium falciparum and Plasmodium vivax, rely on two distinct host cell surface proteins, CD81 and the Scavenger Receptor BI (SR-BI), respectively, to infect hepatocytes. By contrast, CD81 and SR-BI fulfil redundant functions during infection by the rodent parasite P. berghei. Genetic analysis of sporozoite factors reveals the 6-cysteine domain protein P36 as a major parasite determinant of host cell receptor usage. Our data provide molecular insights into the invasion pathways used by different malaria parasites to infect hepatocytes, and establish a functional link between a sporozoite putative ligand and host cell receptors.

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Citations

Mar 13, 2018·FEMS Microbiology Reviews·Carolina Agop-NersesianVolker Theo Heussler
Dec 5, 2017·Frontiers in Microbiology·Meghan ZuckAlexis Kaushansky
Jun 15, 2017·ELife·Oliver Billker
Sep 10, 2020·Cellular Microbiology·Jona KaramWassim Daher
Jun 24, 2020·Malaria Journal·Pradeep A SubramaniVaradharajan Sundaramurthy
Jun 14, 2017·Nature Reviews. Microbiology·Irene Vacca
Feb 23, 2020·Journal of Cell Science·Maria Fátima HortaThiago Castro-Gomes
Dec 14, 2018·Frontiers in Cellular and Infection Microbiology·Silvia A ArredondoStefan H I Kappe
Sep 6, 2019·PLoS Pathogens·Hirdesh Kumar, Niraj H Tolia
Nov 8, 2020·Nature Communications·João Mello-VieiraMaria M Mota
Jan 23, 2021·The Biochemical Journal·Melanie H DietrichWai-Hong Tham
Feb 17, 2021·Trends in Parasitology·Silvia A ArredondoStefan H I Kappe
Jul 17, 2021·Frontiers in Cellular and Infection Microbiology·Nadia AmanzougagheneJean-François Franetich
Jul 2, 2021·Chemical Reviews·Kamalakannan VijayanAlexis Kaushansky

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Methods Mentioned

BETA
FACS
fluorescence microscopy
flow cytometry
transfection
PCR
genotyping
transgenic

Software Mentioned

Coot
GraphPad Prism
Tasser
GraphPad
Clustal Omega

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