TY - JOUR
T1 - High-dimensional mass cytometry identifies T cell and B cell signatures predicting reduced risk of Plasmodium vivax malaria
AU - Ioannidis, Lisa J.
AU - Pietrzak, Halina M.
AU - Ly, Ann
AU - Utami, Retno A.S.
AU - Eriksson, Emily M.
AU - Studniberg, Stephanie I.
AU - Abeysekera, Waruni
AU - Li-Wai-Suen, Connie S.N.
AU - Sheerin, Dylan
AU - Healer, Julie
AU - Puspitasari, Agatha M.
AU - Apriyanti, Dwi
AU - Coutrier, Farah N.
AU - Poespoprodjo, Jeanne R.
AU - Kenangalem, Enny
AU - Andries, Benediktus
AU - Prayoga, Pak
AU - Sariyanti, Novita
AU - Smyth, Gordon K.
AU - Trianty, Leily
AU - Cowman, Alan F.
AU - Price, Ric N.
AU - Noviyanti, Rintis
AU - Hansen, Diana S.
N1 - 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).
PY - 2021/7/22
Y1 - 2021/7/22
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85111050223&partnerID=8YFLogxK
U2 - 10.1172/jci.insight.148086
DO - 10.1172/jci.insight.148086
M3 - Article
C2 - 34128836
AN - SCOPUS:85111050223
SN - 2379-3708
VL - 6
SP - 1
EP - 18
JO - JCI Insight
JF - JCI Insight
IS - 14
M1 - e148086
ER -