Oral Presentation Lorne Infection and Immunity 2021

High dimensional mass cytometry analysis dissects T cell and B cell heterogeneity in the immune response to Plasmodium vivax malaria and identifies signatures predicting immunity to infection (#28)

Lisa J Ioannidis 1 2 , Halina M Pietrzak 1 2 , Ann Ly 1 2 , Emily M Eriksson 1 2 , Stephanie I Studniberg 1 2 , Tami Utami 1 2 , Connie S Li Wai Suen 1 2 , Waruni Abeysekera 1 2 , Gordon Smyth 1 2 , Marie Trussart 1 2 , Leily Trianty 3 , 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

T follicular helper (TFH) cells and MBCs play a crucial role in the induction, maintenance and recall of antibody responses, which are a key component of clinical immunity to malaria. Previous studies have shown that shown that inflammatory pathways associated with the development of clinical symptoms during acute infection induce alterations in both the composition and function of the TFH and MBC compartments, including up-regulation of the TH1-transcritpion factor T-bet. However, there are conflicting reports on the association of these T-bet+ CD4+ T cells and MBCs with human malaria.

 

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. Our main results identified a specific subset of TH2-like circulating TFH cells strongly associated with protection from infection. Unlike previous reports in P. falciparum infection, class-switched but not IgM+ MBCs appeared to be required for protection. Furthermore, our approach was able to identify distinct T-bet+ sub-populations within the CD4+ T cell and MBC compartments that were associated with either increased or reduced risk of symptomatic and asymptomatic P. vivax infection, supporting the notion that inflammatory responses to malaria are not unanimously detrimental and might also support immune networks contributing to the control of infection.