Mapping immune variation and var gene switching in naive hosts infected with Plasmodium falciparum

Milne, K. et al. (2021) Mapping immune variation and var gene switching in naive hosts infected with Plasmodium falciparum. eLife, 10, e62800. (doi: 10.7554/elife.62800) (PMID:33648633) (PMCID:PMC7924948)

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Regnault, Mr Clement and Barrett, Professor Michael

Creator Roles

Regnault, C.: Data curation, Software, Formal analysis, Validation, Visualization
Barrett, M.: Resources, Supervision, Project administration

• Authors: Milne, K., Ivens, A., Reid, A. J., Lotkowska, M. E., O'Toole, A., Sankaranarayanan, G., Munoz Sandoval, D., Nahrendorf, W., Regnault, C., Edwards, N. J., Silk, S. E., Payne, R. O., Minassian, A. M., Venkatraman, N., Sanders, M. J., Hill, A. V.S., Barrett, M., Berriman, M., Draper, S. J., Rowe, J. A., and Spence, P. J.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences; College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: eLife
• Publisher: eLife Sciences Publications
• ISSN: 2050-084X
• ISSN (Online): 2050-084X
• Copyright Holders: Copyright © 2021 Milne et al.
• First Published: First published in eLife 10: e62800
• Publisher Policy: Reproduced under a Creative Commons License

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
170547		The Wellcome Centre for Molecular Parasitology ( Core Support )	Andrew Waters	Wellcome Trust (WELLCOTR)	104111/Z/14/ZR	III - Parasitology