Plasmodium P36 determines host cell receptor usage during sporozoite invasion

eLife

Jean-François Franetich¹  François Nosten²  Eric Rubinstein³  Thierry Huby⁴  Dominique Mazier⁵  Chiara Andolina⁶  Sylvie Briquet⁷  Julien Lescar⁷  Carine Marinach⁷  Olivier Silvie⁷  Matthieu Tolle⁷  Marion Gransagne⁷  Giulia Manzoni⁷  Thomas F Baumert⁷  Selma Topçu⁷  Mirjam B Zeisel⁷  Morgane Grand⁷  Georges Snounou⁸ 

[1] Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom;Université Paris Sud, Institut André Lwoff, Villejuif, France;Université de Strasbourg, Strasbourg, France;INSERM, U1110, Institut de Recherche sur les Maladies Virales et Hépatiques, Strasbourg, France;INSERM, U935, Villejuif, France;Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand;Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, Centre d’Immunologie et des Maladies Infectieuses, U1135, ERL8255, Paris, France;Sorbonne Universités, UPMC Univ Paris 06, INSERM, Institute of Cardiometabolism and Nutrition, UMR_S 1166, Paris, France;

关键词: malaria;    hepatocyte;    sporozoite;    P. vivax;    P. berghei;    P. yoelii;   

DOI  :  10.7554/eLife.25903

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown