Molecular profiling reveals features of clinical immunity and immunosuppression in asymptomatic P. falciparum malaria

To define the impact of asymptomatic malaria, we pursued a systems approach integrating antibody responses, mass cytometry, and transcriptional profiling of individuals experiencing symptomatic and asymptomatic P. falciparum infection. Defined populations of classical and atypical memory B cells and a TH2 cell bias were associated with reduced risk of clinical malaria. Despite these protective responses, asymptomatic malaria featured an immunosuppressive transcriptional signature with upregulation of pathways involved in the inhibition of T cell function, and CTLA-4 as a predicted regulator in these processes. We performed RNA-seq analysis of bulk PBMCs on a cohort of 17 individuals experiencing either symptomatic (n=6) or asymptomatic (n=5) malaria and healthy immune controls (n=6). Raw data are available upon request, subject to approval by the Walter and Eliza Hall Institutional Data Access Committee ([e-mail]) to ensure preservation of patient confidentiality.