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Title: Age-dependent changes in circulating Tfh cells influence development of functional malaria antibodies in children
Authors: Chan, Jo-Anne
Loughland, Jessica R
de la Parte, Lauren
Okano, Satomi
Ssewanyana, Isaac
Nalubega, Mayimuna
Nankya, Felistas
Musinguzi, Kenneth
Rek, John
Arinaitwe, Emmanuel
Tipping, Peta
Bourke, Peter 
Andrew, Dean
Dooley, Nicholas
SheelaNair, Arya
Wines, Bruce D
Hogarth, P Mark
Beeson, James G
Greenhouse, Bryan
Dorsey, Grant
Kamya, Moses
Hartel, Gunter
Minigo, Gabriela
Feeney, Margaret
Jagannathan, Prasanna
Boyle, Michelle J
Issue Date: 2022
Publisher: Nature Publishing Group
Source: Chan JA, Loughland JR, de la Parte L, Okano S, Ssewanyana I, Nalubega M, Nankya F, Musinguzi K, Rek J, Arinaitwe E, Tipping P, Bourke P, Andrew D, Dooley N, SheelaNair A, Wines BD, Hogarth PM, Beeson JG, Greenhouse B, Dorsey G, Kamya M, Hartel G, Minigo G, Feeney M, Jagannathan P, Boyle MJ. Age-dependent changes in circulating Tfh cells influence development of functional malaria antibodies in children. Nat Commun. 2022 Jul 18;13(1):4159. doi: 10.1038/s41467-022-31880-6. PMID: 35851033; PMCID: PMC9293980.
Journal: Nature communications
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.
Description: Cairns & Hinterland Hospital and Health Service (CHHHS) affiliated author: Peter Bourke
DOI: 10.1038/s41467-022-31880-6
Keywords: Immunological memory;Infection;Malaria
Type: Article
Appears in Sites:Cairns & Hinterland HHS Publications

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