Dataset Information

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.

SUBMITTER: Chan JA

PROVIDER: S-EPMC9293980 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

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

Chan Jo-Anne JA Loughland Jessica R JR de la Parte Lauren L Okano Satomi S Ssewanyana Isaac I Nalubega Mayimuna M Nankya Felistas F Musinguzi Kenneth K Rek John J Arinaitwe Emmanuel E Tipping Peta P Bourke Peter P Andrew Dean D Dooley Nicholas N SheelaNair Arya A Wines Bruce D BD Hogarth P Mark PM Beeson James G JG Greenhouse Bryan B Dorsey Grant G Kamya Moses M Hartel Gunter G Minigo Gabriela G Feeney Margaret M Jagannathan Prasanna P Boyle Michelle J MJ

Nature communications 20220718 1

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 ...[more]

PMID: 35851033

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

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

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