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

Authors
  • Milne, Kathryn1
  • Ivens, Alasdair1, 2
  • Reid, Adam J3
  • Lotkowska, Magda E3
  • O'Toole, Aine2, 4
  • Sankaranarayanan, Geetha3
  • Munoz Sandoval, Diana1, 5
  • Nahrendorf, Wiebke1
  • Regnault, Clement6, 7
  • Edwards, Nick J8
  • Silk, Sarah E8
  • Payne, Ruth O8
  • Minassian, Angela M8
  • Venkatraman, Navin8
  • Sanders, Mandy J3
  • Hill, Adrian Vs8
  • Barrett, Michael6, 7
  • Berriman, Matthew3
  • Draper, Simon J8
  • Rowe, J Alexandra1, 2
  • And 1 more
  • 1 Institute of Immunology and Infection Research, University of Edinburgh, Edinburgh, United Kingdom. , (United Kingdom)
  • 2 Centre for Immunity, Infection and Evolution, University of Edinburgh, Edinburgh, United Kingdom. , (United Kingdom)
  • 3 Wellcome Sanger Institute, Cambridge, United Kingdom. , (United Kingdom)
  • 4 Institute of Evolutionary Biology, University of Edinburgh, Edinburgh, United Kingdom. , (United Kingdom)
  • 5 Instituto de Microbiologia, Universidad San Francisco de Quito, Quito, Ecuador. , (Ecuador)
  • 6 Wellcome Centre for Integrative Parasitology, University of Glasgow, Glasgow, United Kingdom. , (United Kingdom)
  • 7 Glasgow Polyomics, University of Glasgow, Glasgow, United Kingdom. , (United Kingdom)
  • 8 The Jenner Institute, University of Oxford, Oxford, United Kingdom. , (United Kingdom)
Type
Published Article
Journal
eLife
Publisher
"eLife Sciences Organisation, Ltd."
Publication Date
Mar 02, 2021
Volume
10
Identifiers
DOI: 10.7554/eLife.62800
PMID: 33648633
Source
Medline
Keywords
Language
English
License
Unknown

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. © 2021, Milne et al.

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