Background: Infection caused by Plasmodium falciparum and Plasmodium vivax are the major cause of malaria worldwide. While clinical immunity is achieved quicker in P. vivax and P. falciparum through observations in both endemic and experimental settings, the mechanisms are not clearly understood. An important mediator of malaria immunity is CD3+ T cells, targeting the parasites via multiple mechanisms including direct killing, antibody induction, and cytokine secretion. Studies in controlled human malaria challenge (CHMI) have suggested that CD3+ T cells have different activation profiles dependent on the species of infection. However, no studies have been undertaken in natural infection.
Methods: We comprehensively investigated the phenotype, function, TCR repertoire, and transcriptional profiles of CD3+ T cells in uninfected (n = 8) and infected individuals with either P. falciparum (n = 25) or P. vivax (n = 12) malaria from a malaria endemic region in Papua, Indonesia. Phenotypes and cytokine production were examined with multiparametric flow cytometry while transcriptomic profiles were investigated with scRNAseq using combinatorial barcoding approach.
Results: CD4+ T cells and T-follicular helper (Tfh) cell subset were activated during acute P. falciparum and P. vivax malaria, with increased frequency of ICOS+ and Ki67+ cells. Between species, ICOS+ and Ki67+ Tfh cell subsets were skewed to Th1-type and Th2-type in P. falciparum and P. vivax, respectively. Further analysis using scRNAseq on sorted CD3+ T cells identified significant differences in cluster abundance, TCR clonal diversity, and activation profiles during acute infection and between P. falciparum and P. vivax malaria. Further analyses on the scRNAseq data are ongoing.
Conclusions: Our findings will provide important insights into differences in mechanisms of adaptive immunity between P. falciparum and P. vivax infection that will inform malaria vaccine development.