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

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 TriantyAlan F. Cowman, Ric N. Price, Rintis Noviyanti, Diana S. Hansen

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)
35 Downloads (Pure)

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.

Original languageEnglish
Article numbere148086
Pages (from-to)1-18
Number of pages18
JournalJCI Insight
Volume6
Issue number14
DOIs
Publication statusPublished - 22 Jul 2021

Bibliographical note

Funding Information:
This work was performed in part at the Materials Characterisation and Fabrication Platform at the University of Melbourne and the Victorian Node of the Australian National Fabrication Facility. It was supported by the Australian National Health and Medical Research Council (NHMRC) Independent Medical Research Institutes Infrastructure Support Scheme and Project Grants 1058665 and 1137989, the Australian Academy of Science (to DSH), the Victorian Operational Infrastructure Support, and the Ministry of Research and Technology of the Republic of Indonesia. GKS was supported by an NHMRC Fellowship (1154970), and RNP is a Wellcome Trust Senior Fellow in Clinical Science (200909).

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