Host Sterol Supply to Plasmodium Parasites as the Therapeutic Target in Malaria

2016 Fiscal Year Final Research Report

• Project/Area Number: 26461499
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Infectious disease medicine
• Research Institution: The University of Tokyo
• Principal Investigator: ISO-O Naoyuki 東京大学, 医科学研究所, 助教 (80420214)
• Co-Investigator(Renkei-kenkyūsha): KITA Kiyoshi 長崎大学, 熱帯医学グローバルヘルス研究科, 教授 (90134444)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: マラリア / リポ蛋白 / スカベンジャー受容体 / エクソソーム

Outline of Final Research Achievements

In this study, we found a novel feeding pathway for cholesteryl esters by Plasmodium erythrocyte-stage parasites in a form of high density lipoprotein (HDL). Addition of fluorescently-labelled HDL into in vitro culture resulted in an internalization of HDL signal to both parasitized erythrocyte membrane and parasite body. BLT-1, an antagonist for class B scavenger receptors, blocked HDL uptake, and Plasmodium growth in vitro significantly reduced. Reaction with anti-CD36 antibody was positive only with parasitized host erythrocyte membranes and the apical membrane of internal parasites, but not in a CD36-deficient mouse or a mouse with bone marrow transplanted from the CD36-deficient mouse. We also found that double positive exosomes for CD36 and platelet-specific CD41 were detected from infected mouse plasma. In addition, anti-CD41 antibody reacted with parasite membrane, suggesting that CD36 is delivered from host platelets via exosomes.

Free Research Field

脂質代謝学