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

Author:

Milne Kathryn1,Ivens Alasdair12,Reid Adam J3,Lotkowska Magda E3,O'Toole Aine24,Sankaranarayanan Geetha3,Munoz Sandoval Diana15,Nahrendorf Wiebke1,Regnault Clement67,Edwards Nick J8ORCID,Silk Sarah E8,Payne Ruth O8,Minassian Angela M8,Venkatraman Navin8,Sanders Mandy J3,Hill Adrian VS8,Barrett Michael67,Berriman Matthew3ORCID,Draper Simon J8ORCID,Rowe J Alexandra12ORCID,Spence Philip J12ORCID

Affiliation:

1. Institute of Immunology and Infection Research, University of Edinburgh, Edinburgh, United Kingdom

2. Centre for Immunity, Infection and Evolution, University of Edinburgh, Edinburgh, United Kingdom

3. Wellcome Sanger Institute, Cambridge, United Kingdom

4. Institute of Evolutionary Biology, University of Edinburgh, Edinburgh, United Kingdom

5. Instituto de Microbiologia, Universidad San Francisco de Quito, Quito, Ecuador

6. Wellcome Centre for Integrative Parasitology, University of Glasgow, Glasgow, United Kingdom

7. Glasgow Polyomics, University of Glasgow, Glasgow, United Kingdom

8. The Jenner Institute, University of Oxford, Oxford, United Kingdom

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.

Funder

Medical Research Council

Wellcome Trust

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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