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

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 5

Subsets of classical and atypical class-switched MBCs associate with reduced P. vivax parasite burden.

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Subsets of classical and atypical class-switched MBCs associate with red...
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. Percentages of classical MBC (A), activated MBC (B), and atypical MBC (C) subpopulations identified by CyTOF after FlowSOM analysis. Boxes represent the 25th to 75th percentile, whiskers show the range (minimum to maximum), and lines represent the median. The relationship between MBC subpopulations and clinical parameters was determined by Spearman’s rank correlation (D). P. vivax symptomatic (n = 6) and asymptomatic (n = 8) infected individuals as well as healthy immune controls (n = 6) were stained with fluorescent antibodies and analyzed by flow cytometry to assess IgG and IgA expression among IgM–IgD–CXCR5loCCR6lo classical MBCs (E and F), IgM–IgD– activated MBCs (G and H) and IgM–IgD–T-bet+ atypical MBCs (I and J) as well as FcRL5 expression among IgM–IgD–CCR6+T-bet+ atypical MBCs (K). Representative histograms and contour plots are shown. Stacked bars represent the mean ± SEM. Boxes represent the 25th to 75th percentile, whiskers show the range (minimum to maximum), and lines represent the median. CXCR5 and CCR6 expression was also assessed among gated IgM–IgD– classical MBCs (L), and a logistic regression model was used to determine the association between CXCR5 and CCR6 expression levels and the risk of asymptomatic or symptomatic P. vivax infection (M). Symbols represent the odds ratio and vertical lines depict the 95% confidence interval; *P < 0.05, **P < 0.01, ***P < 0.001. Significance was determined by 1-way ANOVA with Holm-Sidak post test or Kruskal-Wallis with Dunn’s multiple-comparison post test (A–C, F, and H), Spearman’s rank correlation (D), or unpaired, 2-tailed t test or Mann-Whitney U test (K). HC, healthy control; AS, asymptomatic; SY, symptomatic.