Identification of host pathogenic factors responsible for development of cerebral malaria

2023 Fiscal Year Final Research Report

• Project/Area Number: 19K07530
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49040:Parasitology-related
• Research Institution: National Institute of Infectious Diseases
• Principal Investigator: Hisaeda Hajime 国立感染症研究所, 寄生動物部, 部長 (50243689)
• Project Period (FY): 2019-04-01 – 2024-03-31
• Keywords: マラリア / 脳マラリア / バイオマーカー

Outline of Final Research Achievements

Malaria is the world's largest infectious disease, causing up to 500,000 deaths, with cerebral malaria accounting for the majority of deaths. In this study, we extracted factors that aggravate the severity of cerebral malaria through analysis of cerebral malaria patient samples, and examined their involvement in a mouse model.
Twenty-eight proteins that increase in cerebral malaria patients and show low levels after treatment were selected as candidates. Among these, we obtained gene-deficient mice for TSLP, IL-33, IL-34, IL-28A, Fgf-1, and MPO, and investigated their involvement in the development of cerebral malaria. MPO contributes to the onset of cerebral malaria, but no other molecules were involved in the onset. The pathogenic mechanism of MPO was suggested to be enhanced adhesion of infected red blood cells to vascular endothelial cells.

Free Research Field

寄生虫学

Academic Significance and Societal Importance of the Research Achievements

開発途上国で社会経済的問題となっているマラリアの病態を理解することはそのコントロールに重要である。本研究では、致死的合併症である脳マラリアの発症に関わる宿主分子を明らかにし、新たな予防法や治療法の基盤となる知見を得ることを目的とした。
ウガンダで得た脳マラリア患者サンプルを用いて、脳マラリアで特異的に増加する蛋白質のうち、６種について遺伝子欠損マウスを得た。唯一、MPOが発症に関与することが明らかにできた。今後は、MPOによる脳マラリア発症メカニズムを理解し、治療法への応用が期待できる。