Milne, K., Ivens, A., Reid, A.J. et al. (18 more authors) (2021) Mapping immune variation and var gene switching in naive hosts infected with Plasmodium falciparum. eLife, 10. e62800. ISSN 2050-084X
Abstract
Falciparum malaria is clinically heterogeneous and the relative contribution of parasite and host in shaping disease severity remains unclear. We explored the interaction between inflammation and parasite variant surface antigen (VSA) expression, asking whether this relationship underpins the variation observed in controlled human malaria infection (CHMI). We uncovered marked heterogeneity in the host response to blood challenge; some volunteers remained quiescent, others triggered interferon-stimulated inflammation and some showed transcriptional evidence of myeloid cell suppression. Significantly, only inflammatory volunteers experienced hallmark symptoms of malaria. When we tracked temporal changes in parasite VSA expression to ask whether variants associated with severe disease rapidly expand in naive hosts, we found no transcriptional evidence to support this hypothesis. These data indicate that parasite variants that dominate severe malaria do not have an intrinsic growth or survival advantage; instead, they presumably rely upon infection-induced changes in their within-host environment for selection.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2021, Milne et al. This article is distributed under the terms of the Creative Commons Attribution License, (http://creativecommons.org/licenses/by/4.0/) which permits unrestricted use and redistribution provided that the original author and source are credited. |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > Department of Infection and Immunity (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 15 Mar 2021 12:29 |
Last Modified: | 17 Mar 2021 04:52 |
Status: | Published |
Publisher: | eLife Sciences Publications, Ltd |
Refereed: | Yes |
Identification Number: | 10.7554/elife.62800 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:171761 |