Erythrocyte CD55 mediates the internalization of Plasmodium falciparum parasites

Abstract
Data availability
Article and author information
Metrics

Abstract

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 point 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.

Data availability

All data generated or analyzed during this study are included in the manuscript and supporting files.

Article and author information

Author details

Bikash Shakya

Pediatrics, Stanford University School of Medicine, Stanford, United States

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-9100-0660
Saurabh D Patel

Zuckerman Institute, Columbia University, New York City, United States

Competing interests
The authors declare that no competing interests exist.
Yoshihiko Tani

Osaka Blood Center, Japanese Red Cross Osaka, Osaka, Japan

Competing interests
The authors declare that no competing interests exist.
Elizabeth S Egan

Pediatrics and Microbiology & Immunology, Stanford University School of Medicine, Stanford, United States

For correspondence
eegan@stanford.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-2112-7700

Funding

NIH Office of the Director (DP2HL13718601)

Elizabeth S Egan

National Institute of Diabetes and Digestive and Kidney Diseases (5T32DK098132-05)

Bikash Shakya

Stanford Maternal and Child Health Research Institute

Elizabeth S Egan

Donald E. and Delia B. Baxter Foundation

Elizabeth S Egan

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.