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

• DOI: 10.7554/elife.62800
• Publication Date: 2021-03-02T00:00:25Z
• Authors: Kathryn Milne; Alasdair Ivens; Adam J Reid; Magda E Lotkowska; Aine O'Toole; Geetha Sankaranar...; Diana Munoz Sandoval; Wiebke Nahrendorf; Clement Regnault; Nick J Edwards; Sarah E Silk; Ruth O Payne; Angela M Minassian; Navin Venkatraman; Mandy J Sanders; Adrian VS Hill; Michael Barrett; Matthew Berriman; Simon J Draper; J Alexandra Rowe; Philip J Spence
• Keywords: Antigenic variation

Falciparum malaria is clinically heterogeneous and the relative contribution of parasite host in shaping disease severity remains unclear. We explored interaction between inflammation variant surface antigen (VSA) expression, asking whether this relationship underpins variation observed controlled human infection (CHMI). uncovered marked heterogeneity response to blood challenge; some volunteers remained quiescent, others triggered interferon-stimulated showed transcriptional evidence myeloid cell suppression. Significantly, only inflammatory experienced hallmark symptoms malaria. When we tracked temporal changes VSA expression ask variants associated with severe rapidly expand naive hosts, found no support hypothesis. These data indicate that dominate do not have an intrinsic growth or survival advantage; instead, they presumably rely upon infection-induced their within-host environment for selection.