Erythrocyte CD55 mediates the internalization of Plasmodium falciparum parasites
Invasion of human erythrocytes by the malaria parasite Plasmodium falciparum is a multi-step process. Previously, a forward genetic screen for P. falciparum host factors identified erythrocyte CD55 as essential for invasion, but its specific role and how it interfaces with the other factors that med...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2021-05-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/61516 |
| _version_ | 1829096899665199104 |
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| author | Bikash Shakya Saurabh D Patel Yoshihiko Tani Elizabeth S Egan |
| author_facet | Bikash Shakya Saurabh D Patel Yoshihiko Tani Elizabeth S Egan |
| author_sort | Bikash Shakya |
| collection | DOAJ |
| description | Invasion of human erythrocytes by the malaria parasite Plasmodium falciparum is a multi-step process. Previously, a forward genetic screen for P. falciparum host factors identified erythrocyte CD55 as essential for invasion, but its specific role and how it interfaces with the other factors that mediate this complex process are unknown. Using CRISPR-Cas9 editing, antibody-based inhibition, and live cell imaging, here we show that CD55 is specifically required for parasite internalization. Pre-invasion kinetics, erythrocyte deformability, and echinocytosis were not influenced by CD55, but entry was inhibited when CD55 was blocked or absent. Visualization of parasites attached to CD55-null erythrocytes points to a role for CD55 in stability and/or progression of the moving junction. Our findings demonstrate that CD55 acts after discharge of the parasite’s rhoptry organelles, and plays a unique role relative to all other invasion receptors. As the requirement for CD55 is strain-transcendent, these results suggest that CD55 or its interacting partners may hold potential as therapeutic targets for malaria. |
| first_indexed | 2024-04-11T09:05:09Z |
| format | Article |
| id | doaj.art-9b8b2de9edfa408d94e03f8c93304f5c |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T09:05:09Z |
| publishDate | 2021-05-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-9b8b2de9edfa408d94e03f8c93304f5c2022-12-22T04:32:40ZengeLife Sciences Publications LtdeLife2050-084X2021-05-011010.7554/eLife.61516Erythrocyte CD55 mediates the internalization of Plasmodium falciparum parasitesBikash Shakya0https://orcid.org/0000-0001-9100-0660Saurabh D Patel1https://orcid.org/0000-0002-5738-3175Yoshihiko Tani2Elizabeth S Egan3https://orcid.org/0000-0002-2112-7700Departments of Pediatrics and Microbiology & Immunology, Stanford University School of Medicine, Stanford, United StatesZuckerman Institute, Columbia University, New York City, United StatesJapanese Red Cross Osaka Blood Center, Osaka, JapanDepartments of Pediatrics and Microbiology & Immunology, Stanford University School of Medicine, Stanford, United StatesInvasion of human erythrocytes by the malaria parasite Plasmodium falciparum is a multi-step process. Previously, a forward genetic screen for P. falciparum host factors identified erythrocyte CD55 as essential for invasion, but its specific role and how it interfaces with the other factors that mediate this complex process are unknown. Using CRISPR-Cas9 editing, antibody-based inhibition, and live cell imaging, here we show that CD55 is specifically required for parasite internalization. Pre-invasion kinetics, erythrocyte deformability, and echinocytosis were not influenced by CD55, but entry was inhibited when CD55 was blocked or absent. Visualization of parasites attached to CD55-null erythrocytes points to a role for CD55 in stability and/or progression of the moving junction. Our findings demonstrate that CD55 acts after discharge of the parasite’s rhoptry organelles, and plays a unique role relative to all other invasion receptors. As the requirement for CD55 is strain-transcendent, these results suggest that CD55 or its interacting partners may hold potential as therapeutic targets for malaria.https://elifesciences.org/articles/61516erythrocytesmalariainvasion |
| spellingShingle | Bikash Shakya Saurabh D Patel Yoshihiko Tani Elizabeth S Egan Erythrocyte CD55 mediates the internalization of Plasmodium falciparum parasites eLife erythrocytes malaria invasion |
| title | Erythrocyte CD55 mediates the internalization of Plasmodium falciparum parasites |
| title_full | Erythrocyte CD55 mediates the internalization of Plasmodium falciparum parasites |
| title_fullStr | Erythrocyte CD55 mediates the internalization of Plasmodium falciparum parasites |
| title_full_unstemmed | Erythrocyte CD55 mediates the internalization of Plasmodium falciparum parasites |
| title_short | Erythrocyte CD55 mediates the internalization of Plasmodium falciparum parasites |
| title_sort | erythrocyte cd55 mediates the internalization of plasmodium falciparum parasites |
| topic | erythrocytes malaria invasion |
| url | https://elifesciences.org/articles/61516 |
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