Egan Elizabeth S, Jiang Rays H Y, Moechtar Mischka A, Barteneva Natasha S, Weekes Michael P, Nobre Luis V, Gygi Steven P, Paulo Joao A, Frantzreb Charles, Tani Yoshihiko, Takahashi Junko, Watanabe Seishi, Goldberg Jonathan, Paul Aditya S, Brugnara Carlo, Root David E, Wiegand Roger C, Doench John G, Duraisingh Manoj T
Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, MA, USA. Division of Infectious Diseases, Boston Children's Hospital, Boston, MA, USA.
Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, MA, USA. Department of Global Health and Center for Drug Discovery and Innovation, University of South Florida, Tampa, FL, USA.
Science. 2015 May 8;348(6235):711-4. doi: 10.1126/science.aaa3526.
Efforts to identify host determinants for malaria have been hindered by the absence of a nucleus in erythrocytes, which precludes genetic manipulation in the cell in which the parasite replicates. We used cultured red blood cells derived from hematopoietic stem cells to carry out a forward genetic screen for Plasmodium falciparum host determinants. We found that CD55 is an essential host factor for P. falciparum invasion. CD55-null erythrocytes were refractory to invasion by all isolates of P. falciparum because parasites failed to attach properly to the erythrocyte surface. Thus, CD55 is an attractive target for the development of malaria therapeutics. Hematopoietic stem cell-based forward genetic screens may be valuable for the identification of additional host determinants of malaria pathogenesis.
由于红细胞中没有细胞核，这使得在寄生虫复制的细胞中进行基因操作变得不可能，因此确定疟疾宿主决定因素的努力受到了阻碍。我们使用源自造血干细胞的培养红细胞对恶性疟原虫的宿主决定因素进行正向遗传筛选。我们发现CD55是恶性疟原虫入侵的必需宿主因子。缺乏CD55的红细胞对所有恶性疟原虫分离株的入侵均具有抗性，因为寄生虫无法正确附着于红细胞表面。因此，CD55是疟疾治疗药物开发的一个有吸引力的靶点。基于造血干细胞的正向遗传筛选对于鉴定疟疾发病机制的其他宿主决定因素可能具有重要价值。
