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High-dimensional mass cytometry identifies T cell and B cell signatures predicting reduced risk of Plasmodium vivax malaria
Lisa J. Ioannidis, … , Rintis Noviyanti, Diana S. Hansen
Lisa J. Ioannidis, … , Rintis Noviyanti, Diana S. Hansen
Published June 15, 2021
Citation Information: JCI Insight. 2021;6(14):e148086. https://doi.org/10.1172/jci.insight.148086.
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Research Article Immunology Infectious disease

High-dimensional mass cytometry identifies T cell and B cell signatures predicting reduced risk of Plasmodium vivax malaria

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Abstract

IFN-γ–driven responses to malaria have been shown to modulate the development and function of T follicular helper (TFH) cells and memory B cells (MBCs), with conflicting evidence of their involvement in the induction of antibody responses required to achieve clinical immunity and their association with disease outcomes. Using high-dimensional single-cell mass cytometry, we identified distinct populations of TH1-polarized CD4+ T cells and MBCs expressing the TH1-defining transcription factor T-bet, associated with either increased or reduced risk of Plasmodium vivax (P. vivax) malaria, demonstrating that inflammatory responses to malaria are not universally detrimental for infection. Furthermore, we found that, whereas class-switched but not IgM+ MBCs were associated with a reduced risk of symptomatic malaria, populations of TH1 cells with a stem central memory phenotype, TH17 cells, and T regulatory cells were associated with protection from asymptomatic infection, suggesting that activation of cell-mediated immunity might also be required to control persistent P. vivax infection with low parasite burden.

Authors

Lisa J. Ioannidis, Halina M. Pietrzak, Ann Ly, Retno A.S. Utami, Emily M. Eriksson, Stephanie I. Studniberg, Waruni Abeysekera, Connie S.N. Li-Wai-Suen, Dylan Sheerin, Julie Healer, Agatha M. Puspitasari, Dwi Apriyanti, Farah N. Coutrier, Jeanne R. Poespoprodjo, Enny Kenangalem, Benediktus Andries, Pak Prayoga, Novita Sariyanti, Gordon K. Smyth, Leily Trianty, Alan F. Cowman, Ric N. Price, Rintis Noviyanti, Diana S. Hansen

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Figure 6

Memory CD4+ T cell population from diverse lineages and class-switched MBCs predict reduced risk of P. vivax malaria.

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Memory CD4+ T cell population from diverse lineages and class-switched M...
PBMCs from P. vivax symptomatic (n = 11) and asymptomatic (n = 19) infected individuals as well as healthy immune controls (n = 24) were stained with a panel of metal-labeled antibodies and analyzed by CyTOF. Unsupervised hierarchical clustering heatmap showing the frequency of cell populations that were differentially abundant between healthy immune controls and symptomatic P. vivax–infected individuals (A). Spearman’s correlation networks were used to examine the relationship between cell populations that were either reduced (B) or increased (C) in healthy immune controls compared with individuals with a symptomatic infection. Logistic regression models were used to determine the association between cell frequencies and the risk of asymptomatic or symptomatic P. vivax infection (D). Symbols represent the odds ratio and vertical lines depict the 95% confidence interval. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001. The automated machine learning workflow SIMON was used to identify cell populations that best predict protection from both asymptomatic and symptomatic infection. Receiver operating characteristic (ROC) curves for classifying individuals with either a symptomatic (E) or asymptomatic (F) infection based on the relative frequency of each cell population. Colored curves represent the 3 best performing models. Top-ranked features (variable importance score > 85%) of symptomatic (G) and asymptomatic infection (H). Bars represent the variable importance score for each feature. HC, healthy control; AS, asymptomatic; SY, symptomatic.

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