Dantzler, K. W. et al. (2019) Naturally acquired immunity against immature Plasmodium falciparum gametocytes. Science Translational Medicine, 11(495), eaav3963. (doi: 10.1126/scitranslmed.aav3963) (PMID:31167926) (PMCID:PMC6653583)
|
Text
188541.pdf - Accepted Version 5MB |
Abstract
The recent decline in global malaria burden has stimulated efforts toward Plasmodium falciparum elimination. Understanding the biology of malaria transmission stages may provide opportunities to reduce or prevent onward transmission to mosquitoes. Immature P. falciparum transmission stages, termed stages I to IV gametocytes, sequester in human bone marrow before release into the circulation as mature stage V gametocytes. This process likely involves interactions between host receptors and potentially immunogenic adhesins on the infected red blood cell (iRBC) surface. Here, we developed a flow cytometry assay to examine immune recognition of live gametocytes of different developmental stages by naturally exposed Malawians. We identified strong antibody recognition of the earliest immature gametocyte-iRBCs (giRBCs) but not mature stage V giRBCs. Candidate surface antigens (n = 30), most of them shared between asexual- and gametocyte-iRBCs, were identified by mass spectrometry and mouse immunizations, as well as correlations between responses by protein microarray and flow cytometry. Naturally acquired responses to a subset of candidate antigens were associated with reduced asexual and gametocyte density, and plasma samples from malaria-infected individuals were able to induce immune clearance of giRBCs in vitro. Infected RBC surface expression of select candidate antigens was validated using specific antibodies, and genetic analysis revealed a subset with minimal variation across strains. Our data demonstrate that humoral immune responses to immature giRBCs and shared iRBC antigens are naturally acquired after malaria exposure. These humoral immune responses may have consequences for malaria transmission potential by clearing developing gametocytes, which could be leveraged for malaria intervention.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Ngotho, Dr Priscilla and Marti, Professor Matthias and Seydel, Dr Karl and Lemgruber Soares, Dr Leandro and De Niz, Dr Mariana |
| Authors: | Dantzler, K. W., Ma, S., Ngotho, P., Stone, W. J.R., Tao, D., Rijpma, S., De Niz, M., Nilsson Bark, S. K., Jore, M. M., Raaijmakers, T. K., Early, A. M., Ubaida-Mohien, C., Lemgruber, L., Campo, J. J., Teng, A. A., Le, T. Q., Walker, C. L., Hermand, P., Deterre, P., Davies, D. H., Felgner, P., Morlais, I., Wirth, D. F., Neafsey, D. E., Dinglasan, R. R., Laufer, M., Huttenhower, C., Seydel, K., Taylor, T., Bousema, T., and Marti, M. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
| Journal Name: | Science Translational Medicine |
| Publisher: | American Association for the Advancement of Science |
| ISSN: | 1946-6234 |
| ISSN (Online): | 1946-6242 |
| Copyright Holders: | Copyright © 2019 The Authors |
| First Published: | First published in Science Translational Medicine 11(495):eaav3963 |
| Publisher Policy: | Reproduced in accordance with the copyright policy of the publisher |
University Staff: Request a correction | Enlighten Editors: Update this record
Funder and Project Information
Funder and Project Information