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Malaria. A forward genetic screen identifies erythrocyte CD55 as essential for Plasmodium falciparum invasion
Elizabeth S Egan1, Rays H Y Jiang2, Mischka A Moechtar3
1Department 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.
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.
Insights
Scientists identified CD55 as a crucial host factor for Plasmodium falciparum malaria parasite invasion. This discovery, using hematopoietic stem cells, offers a new target for developing malaria therapeutics and understanding disease pathogenesis.
Area of Science:
- Malariology
- Hematology
- Genetics
Background:
- Identifying host factors for malaria parasite Plasmodium falciparum is challenging due to the lack of a nucleus in mature red blood cells, preventing genetic manipulation.
- Previous research faced limitations in studying host-parasite interactions within erythrocytes.
Purpose of the Study:
- To conduct a forward genetic screen for Plasmodium falciparum host determinants using a novel red blood cell model.
- To identify essential host factors required for P. falciparum invasion and replication.
Main Methods:
- Utilized cultured red blood cells derived from hematopoietic stem cells for genetic screening.
- Performed a forward genetic screen to identify host determinants of P. falciparum invasion.
Main Results:
- Discovered that CD55 is an essential host factor for P. falciparum invasion.
- CD55-null erythrocytes demonstrated complete resistance to invasion by all tested P. falciparum isolates.
- Parasite attachment to the erythrocyte surface was significantly impaired in the absence of CD55.
Conclusions:
- CD55 is a critical host determinant for P. falciparum invasion, making it a promising target for novel malaria therapeutics.
- Hematopoietic stem cell-based genetic screens represent a powerful approach for discovering additional host factors in malaria pathogenesis.
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