@article{cc45fb70aa4547dd8de49f2b4f5a6ad5,
title = "Age-dependent changes in circulating Tfh cells influence development of functional malaria antibodies in children",
abstract = "T-follicular helper (Tfh) cells are key drivers of antibodies that protect from malaria. However, little is known regarding the host and parasite factors that influence Tfh and functional antibody development. Here, we use samples from a large cross-sectional study of children residing in an area of high malaria transmission in Uganda to characterize Tfh cells and functional antibodies to multiple parasites stages. We identify a dramatic re-distribution of the Tfh cell compartment with age that is independent of malaria exposure, with Th2-Tfh cells predominating in early childhood, while Th1-Tfh cell gradually increase to adult levels over the first decade of life. Functional antibody acquisition is age-dependent and hierarchical acquired based on parasite stage, with merozoite responses followed by sporozoite and gametocyte antibodies. Antibodies are boosted in children with current infection, and are higher in females. The children with the very highest antibody levels have increased Tfh cell activation and proliferation, consistent with a key role of Tfh cells in antibody development. Together, these data reveal a complex relationship between the circulating Tfh compartment, antibody development and protection from malaria.",
keywords = "Adult, Antibodies, Protozoan, Child, preschool child, Cross-Sectional Studies, Female, Humans, Malaria, T follicular helper cells, T-Lymphocytes, Helper-Inducer, Uganda, Tfh cell;",
author = "Chan, {Jo Anne} and Loughland, {Jessica R.} and {de la Parte}, Lauren and Satomi Okano and Isaac Ssewanyana and Mayimuna Nalubega and Felistas Nankya and Kenneth Musinguzi and John Rek and Emmanuel Arinaitwe and Peta Tipping and Peter Bourke and Dean Andrew and Nicholas Dooley and Arya SheelaNair and Wines, {Bruce D.} and Hogarth, {P. Mark} and Beeson, {James G.} and Bryan Greenhouse and Grant Dorsey and Moses Kamya and Gunter Hartel and Gabriela Minigo and Margaret Feeney and Prasanna Jagannathan and Boyle, {Michelle J.}",
note = "Funding Information: We thank Australian Red Cross Blood Service for providing malaria na{\"i}ve samples. We thank all staff of Infectious Disease Research Collaboration, Uganda. We thank all study volunteers and their guardians. This work was supported by the National Health and Medical Research Council of Australia (Early Career Fellowship 1125656, Career Development Award 1141278, Project Grant 1125656 and Ideas Grant 1181932 to M.J.B.; Senior Research Fellowship 1077636 to J.G.B.). Additional support was provided by NIH (U19 A108974 to G.D., and U01 AI150741 to P.J.). The Burnet Institute is supported by the National Health and Medical Research Council for Independent Research Institutes Infrastructure Support Scheme and the Victorian State Government Operational Infrastructure Support. Funding Information: We thank Australian Red Cross Blood Service for providing malaria na{\"i}ve samples. We thank all staff of Infectious Disease Research Collaboration, Uganda. We thank all study volunteers and their guardians. This work was supported by the National Health and Medical Research Council of Australia (Early Career Fellowship 1125656, Career Development Award 1141278, Project Grant 1125656 and Ideas Grant 1181932 to M.J.B.; Senior Research Fellowship 1077636 to J.G.B.). Additional support was provided by NIH (U19 A108974 to G.D., and U01 AI150741 to P.J.). The Burnet Institute is supported by the National Health and Medical Research Council for Independent Research Institutes Infrastructure Support Scheme and the Victorian State Government Operational Infrastructure Support. Publisher Copyright: {\textcopyright} 2022, The Author(s).",
year = "2022",
month = jul,
day = "18",
doi = "10.1038/s41467-022-31880-6",
language = "English",
volume = "13",
pages = "1--15",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}