Oral Presentation 8th International Conference on Plasmodium vivax Research 2022

High dimensional single cell mass cytometry identifies T cell and B cell signatures predicting reduced risk of Plasmodium vivax malaria (80115)

Lisa J Ioannidis 1 2 , Halina M Pietrzak 1 2 , Ann Ly 1 2 , Retno AS Utami 1 2 3 , Emily M Eriksson 1 2 , Stephanie I Studniberg 1 2 , Waruni Abeysekera 1 2 , Connie SN Li-Wai-Suen 1 2 , Dylan Sheerin 1 2 , Julie Healer 1 2 , Agatha M Puspitasari 3 , Dwi Apriyanti 3 , Farah N Coutrier 3 , Jeanne R Poespoprodjo 4 , Enny Kenangalem 4 , Benediktus Andries 4 , Pak Prayoga 4 , Novita Sariyanti 4 , Gordon K Symth 1 5 , Leily Trianty 3 , Alan F Cowman 1 2 , Ric N Price 6 7 8 , Rintis Noviyanti 3 , Diana S Hansen 1 2
  1. The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia
  2. The Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia
  3. The Eijkman Institute for Molecular Biology, Jakarta, Indonesia
  4. Papuan Health and Community Foundation, Papua, Indonesia
  5. School of Mathematics and Statistics, The University of Melbourne, Parkville, Victoria, Australia
  6. Global and Tropical Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, Northern Territory, Australia
  7. Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
  8. Mahidol-Oxford Tropical Medicine Research Unit, Mahidol University, Bangkok, Thailand

IFN-γ-driven responses to malaria have long been viewed as a double-edged sword, as they appear to contribute to the control of parasitemia but also play a role in the development of clinical symptoms. Recent studies have shown that this pathway modulates the development and function of T follicular helper (TFH) cells and memory B cells (MBCs) during acute malaria, with conflicting reports on their involvement in the induction of antibody responses required to achieve clinical immunity and their association with disease outcomes.

 

Most of our current knowledge on immune responses to malaria are derived from bulk population data, which assumes that cells belonging to the same sub-type are homogeneous. These bulk-like analyses often oversimplify the immune response, leading to the conflicting view that the same CD4+ T cell and MBC responses appear to associate with opposite infection outcomes. To address this issue, we used high dimensional single cell mass cytometry to untangle the complexity of the CD4+ T cell and MBC response induced in response to Plasmodium vivax infection. This approach allowed us to identify distinct populations of TH1-polarized CD4+ T cells and MBCs expressing the TH1-defining transcription factor T-bet predicting either increased or reduced risk of P. vivax malaria, demonstrating that inflammatory responses to malaria are not universally detrimental. Furthermore, while class-switched MBCs were identified as predictors of reduced risk of symptomatic malaria, specific subsets of CD4+ T cells with different polarization status appeared to be associated with protection from asymptomatic infection. These results suggest that whereas class-switched MBCs and humoral immunity are important for the control of symptomatic P. vivax malaria, cellular responses mediated by CD4+T cells are required for the control of asymptomatic infection of low parasite burden.