Journal article

Th2-like T Follicular Helper Cells Promote Functional Antibody Production during Plasmodium falciparum Infection

Jo-Anne Chan, Jessica R Loughland, Fabian de Labastida Rivera, Arya SheelaNair, Dean W Andrew, Nicholas L Dooley, Bruce D Wines, Fiona H Amante, Lachlan Webb, P Mark Hogarth, James S McCarthy, James G Beeson, Christian R Engwerda, Michelle J Boyle

CELL REPORTS MEDICINE | ELSEVIER | Published : 2020

Abstract

CD4+ T follicular helper cells (Tfh) are key drivers of antibody development. During Plasmodium falciparum malaria in children, the activation of Tfh is restricted to the Th1 subset and not associated with antibody levels. To identify Tfh subsets that are associated with antibody development in malaria, we assess Tfh and antibodies longitudinally in human volunteers with experimental P. falciparum infection. Tfh cells activate during infection, with distinct dynamics in different Tfh subsets. Th2-Tfh cells activate early, during peak infection, while Th1-Tfh cells activate 1 week after peak infection and treatment. Th2-Tfh cell activation is associated with the functional breadth and magnitu..

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Grants

Awarded by National Health and Medical Research Council of Australia


Awarded by National Health and Medical Research Council of Australia (Australian Centre for Research Excellence in Malaria Elimination)


Funding Acknowledgements

RBC and human serum used for parasite culture and naive control sera were provided by the Australian Red Cross Blood Bank (Melbourne). We acknowledge Robin Anders for providing the recombinant MSP2 antigen. We thank the participants involved in the malaria volunteer infection studies, Q-Pharm staff, and Medicine for Malaria Venture for funding the IBSM studies. The graphical abstract was created with BioRender.com. This work was supported by the National Health and Medical Research Council of Australia (program grant 1132975 to J.S.M. and C.R.E.; Practitioner Fellowship 1135955 to J.S.M., Senior Research Fellowship 1154265 to C.R.E., Career Development Award 1141278, Project Grant 1125656, and Ideas Grant 1181932 to M.J.B.; Program Grant 290208, Senior Research Fellowship 1077636 to J.G.B.; Australian Centre for Research Excellence in Malaria Elimination 1134989 to J.G.B. and J.S.M.); and the Jim and Margaret Beever Fellowship to J.-A.C. The Burnet Institute is supported by the NHMRC for Independent Research Institutes Infrastructure Support Scheme and the Victorian State Government Operational Infrastructure Support.