Adults with Plasmodium falciparum malaria have higher magnitude and quality of circulating T-follicular helper cells compared to children
Damian. A. Oyong,
Jessica. R. Loughland,
Megan. S.F. Soon,
Jo-Anne Chan,
Dean Andrew,
Bruce D. Wines,
P. Mark Hogarth,
Stuart D. Olver,
Alika D. Collinge,
Antiopi Varelias,
James G. Beeson,
Enny Kenangalem,
Ric N. Price,
Nicholas M. Anstey,
Gabriela Minigo,
Michelle J. Boyle
Affiliations
Damian. A. Oyong
Global and Tropical Health Division, Menzies School of Health Research, Darwin, Northern Territory, Australia; Charles Darwin University, Darwin, NT, Australia
Jessica. R. Loughland
Global and Tropical Health Division, Menzies School of Health Research, Darwin, Northern Territory, Australia; QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia
Megan. S.F. Soon
QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia
Jo-Anne Chan
Burnet Institute, Melbourne, VIC, Australia; Department of Immunology, Central Clinical School, Monash University, VIC, Australia; Department of Medicine, University of Melbourne, VIC, Australia
Dean Andrew
QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia
Bruce D. Wines
Burnet Institute, Melbourne, VIC, Australia; Department of Immunology, Central Clinical School, Monash University, VIC, Australia; Department of Clinical Pathology, University of Melbourne, VIC, Australia
P. Mark Hogarth
Burnet Institute, Melbourne, VIC, Australia; Department of Immunology, Central Clinical School, Monash University, VIC, Australia; Department of Clinical Pathology, University of Melbourne, VIC, Australia
Stuart D. Olver
QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia
Alika D. Collinge
QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia
Antiopi Varelias
QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia; Faculty of Medicine, The University of Queensland, QLD, Australia
James G. Beeson
Burnet Institute, Melbourne, VIC, Australia; Department of Medicine, University of Melbourne, VIC, Australia; Department of Microbiology, Monash University, VIC, Australia
Enny Kenangalem
Timika Malaria Research Program, Papuan Health and Community Development Foundation, Timika, Papua, Indonesia; District Health Authority, Timika, Papua, Indonesia
Ric N. Price
Global and Tropical Health Division, Menzies School of Health Research, Darwin, Northern Territory, Australia; Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK; Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
Nicholas M. Anstey
Global and Tropical Health Division, Menzies School of Health Research, Darwin, Northern Territory, Australia
Gabriela Minigo
Global and Tropical Health Division, Menzies School of Health Research, Darwin, Northern Territory, Australia; Charles Darwin University, Darwin, NT, Australia
Michelle J. Boyle
Global and Tropical Health Division, Menzies School of Health Research, Darwin, Northern Territory, Australia; QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia; Burnet Institute, Melbourne, VIC, Australia; Faculty of Medicine, The University of Queensland, QLD, Australia; Corresponding author. Human Malaria Immunology Group, QIMR Berghofer, 300 Herston Rd, 4006 Brisbane City, QLD, Australia. Phone: +61 7 3845 3726
Summary: Background: Protective malarial antibodies are acquired more rapidly in adults than children, independently of cumulative exposure, however the cellular responses mediating these differences are unknown. CD4 T-follicular helper (Tfh) cells have key roles in inducing antibodies, with Th2-Tfh cell activation associated with antibody development in malaria. Whether Tfh cell activation in malaria is age dependent is unknown and no studies have compared Tfh cell activation in children and adults with malaria. Methods: We undertook a comprehensive study of Tfh cells, along with B cells and antibody induction in children and adults with malaria. Activation and proliferation of circulating Tfh (cTfh) cell subsets was measured ex vivo and parasite-specific Tfh cell frequencies and functions studied with Activation Induced Marker (AIM) assays and intracellular cytokine staining. Findings: During acute malaria, the magnitude of cTfh cell activation was higher in adults than in children and occurred across all cTfh cell subsets in adults but was restricted only to the Th1-cTfh subset in children. Further, adults had higher levels of parasite-specific cTfh cells, and cTfh cells which produced more Th2-Tfh associated cytokine IL-4. Consistent with a role of higher Tfh cell activation in rapid immune development in adults, adults had higher activation of B cells during infection and higher induction of antibodies 7 and 28 days after malaria compared to children. Interpretation: Our data provide evidence that age impacts Tfh cell activation during malaria, and that these differences may influence antibody induction after treatment. Findings have important implications for vaccine development in children. Funding: This word was supported by the National Health and Medical Research Council of Australia, Wellcome Trust, Charles Darwin University Menzies School of Health Research, Channel 7 Children's Research Foundation, and National Health Institute.
