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Science. 2015 May 8;348(6235):711-4. doi: 10.1126/science.aaa3526.

Malaria. A forward genetic screen identifies erythrocyte CD55 as essential for Plasmodium falciparum invasion.

Author information

1
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.
2
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.
3
Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, MA, USA.
4
Department of Pediatrics, Harvard Medical School and Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, USA.
5
Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK.
6
Department of Cell Biology, Harvard Medical School, Boston, MA, USA.
7
Japanese Red Cross Kinki Block Blood Center, Osaka, Japan.
8
Japanese Red Cross Kyushu Block Blood Center, Fukuoka, Japan.
9
Department of Laboratory Medicine, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.
10
The Broad Institute of Harvard and Massachussetts Insititute of Technology, Cambridge, MA, USAA.
11
Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, MA, USA. The Broad Institute of Harvard and Massachussetts Insititute of Technology, Cambridge, MA, USAA. mduraisi@hsph.harvard.edu.

Abstract

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.

PMID:
25954012
PMCID:
PMC4465434
DOI:
10.1126/science.aaa3526
[Indexed for MEDLINE]
Free PMC Article

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