Age-dependent changes in circulating Tfh cells influence development of functional malaria antibodies in children

Jo Anne Chan, Jessica R. Loughland, Lauren de la Parte, Satomi Okano, Isaac Ssewanyana, Mayimuna Nalubega, Felistas Nankya, Kenneth Musinguzi, John Rek, Emmanuel Arinaitwe, Peta Tipping, Peter Bourke, Dean Andrew, Nicholas Dooley, Arya SheelaNair, Bruce D. Wines, P. Mark Hogarth, James G. Beeson, Bryan Greenhouse, Grant DorseyMoses Kamya, Gunter Hartel, Gabriela Minigo, Margaret Feeney, Prasanna Jagannathan, Michelle J. Boyle

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number4159
Pages (from-to)1-15
Number of pages15
JournalNature Communications
Volume13
Issue number1
DOIs
Publication statusPublished - 18 Jul 2022

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