Adults with Plasmodium falciparum malaria have higher magnitude and quality of circulating T-follicular helper cells compared to children
Issued Date
2022-01-01
Resource Type
eISSN
23523964
Scopus ID
2-s2.0-85121977415
Pubmed ID
34968760
Journal Title
eBioMedicine
Volume
75
Rights Holder(s)
SCOPUS
Bibliographic Citation
eBioMedicine Vol.75 (2022)
Suggested Citation
Oyong D.A., Loughland J.R., Soon M.S.F., Chan J.A., Andrew D., Wines B.D., Hogarth P.M., Olver S.D., Collinge A.D., Varelias A., Beeson J.G., Kenangalem E., Price R.N., Anstey N.M., Minigo G., Boyle M.J. Adults with Plasmodium falciparum malaria have higher magnitude and quality of circulating T-follicular helper cells compared to children. eBioMedicine Vol.75 (2022). doi:10.1016/j.ebiom.2021.103784 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/83935
Title
Adults with Plasmodium falciparum malaria have higher magnitude and quality of circulating T-follicular helper cells compared to children
Author's Affiliation
Faculty of Tropical Medicine, Mahidol University
The University of Queensland
University of Melbourne
Menzies School of Health Research
QIMR Berghofer Medical Research Institute
Monash University
Nuffield Department of Medicine
Charles Darwin University
Burnet Institute
Papuan Health and Community Development Foundation
District Health Authority
The University of Queensland
University of Melbourne
Menzies School of Health Research
QIMR Berghofer Medical Research Institute
Monash University
Nuffield Department of Medicine
Charles Darwin University
Burnet Institute
Papuan Health and Community Development Foundation
District Health Authority
Other Contributor(s)
Abstract
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.