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.

Despite being key drivers of protective antibodies against malaria, little is known regarding the host and parasite factors that influence CD4 T-follicular helper cell and antibody development. Authors utilise samples from a study of children living in an area of high malaria transmission in Uganda, to characterize Tfh cells and functional antibodies to multiple parasites stages.

Details

Title
Age-dependent changes in circulating Tfh cells influence development of functional malaria antibodies in children
Author
Chan, Jo-Anne 1   VIAFID ORCID Logo  ; Loughland, Jessica R. 2 ; de la Parte, Lauren 3 ; Okano, Satomi 4 ; Ssewanyana, Isaac 5 ; Nalubega, Mayimuna 6 ; Nankya, Felistas 7 ; Musinguzi, Kenneth 7 ; Rek, John 7 ; Arinaitwe, Emmanuel 7 ; Tipping, Peta 8 ; Bourke, Peter 9 ; Andrew, Dean 4 ; Dooley, Nicholas 10 ; SheelaNair, Arya 4 ; Wines, Bruce D. 11   VIAFID ORCID Logo  ; Hogarth, P. Mark 11 ; Beeson, James G. 12   VIAFID ORCID Logo  ; Greenhouse, Bryan 13   VIAFID ORCID Logo  ; Dorsey, Grant 13 ; Kamya, Moses 7 ; Hartel, Gunter 4   VIAFID ORCID Logo  ; Minigo, Gabriela 14   VIAFID ORCID Logo  ; Feeney, Margaret 13   VIAFID ORCID Logo  ; Jagannathan, Prasanna 3   VIAFID ORCID Logo  ; Boyle, Michelle J. 15   VIAFID ORCID Logo 

1  Burnet Institute, Melbourne, Australia (GRID:grid.1056.2) (ISNI:0000 0001 2224 8486); Monash University, Department of Immunology, Central Clinical School, Melbourne, Australia (GRID:grid.1002.3) (ISNI:0000 0004 1936 7857); The University of Melbourne, Department of Medicine, Parkville, Australia (GRID:grid.1008.9) (ISNI:0000 0001 2179 088X) 
2  QIMR-Berghofer Medical Research Institute, Herston, Australia (GRID:grid.1049.c) (ISNI:0000 0001 2294 1395); Menzies School of Health Research, Global and Tropical Health Division, Tiwi, Australia (GRID:grid.271089.5) (ISNI:0000 0000 8523 7955) 
3  Stanford University, Department of Medicine, Stanford, USA (GRID:grid.168010.e) (ISNI:0000000419368956) 
4  QIMR-Berghofer Medical Research Institute, Herston, Australia (GRID:grid.1049.c) (ISNI:0000 0001 2294 1395) 
5  Infectious Diseases Research Collaboration, Kampala, Uganda (GRID:grid.463352.5) (ISNI:0000 0004 8340 3103); London School of Hygiene and Tropical Medicine, London, UK (GRID:grid.8991.9) (ISNI:0000 0004 0425 469X) 
6  QIMR-Berghofer Medical Research Institute, Herston, Australia (GRID:grid.1049.c) (ISNI:0000 0001 2294 1395); Infectious Diseases Research Collaboration, Kampala, Uganda (GRID:grid.463352.5) (ISNI:0000 0004 8340 3103); University of Queensland, Faculty of Medicine, Brisbane, Australia (GRID:grid.1003.2) (ISNI:0000 0000 9320 7537) 
7  Infectious Diseases Research Collaboration, Kampala, Uganda (GRID:grid.463352.5) (ISNI:0000 0004 8340 3103) 
8  Menzies School of Health Research, Global and Tropical Health Division, Tiwi, Australia (GRID:grid.271089.5) (ISNI:0000 0000 8523 7955) 
9  Cairns Hospital, Division of Medicine, Manunda, Australia (GRID:grid.413210.5) (ISNI:0000 0004 4669 2727) 
10  QIMR-Berghofer Medical Research Institute, Herston, Australia (GRID:grid.1049.c) (ISNI:0000 0001 2294 1395); Griffith University, Brisbane, Australia (GRID:grid.1022.1) (ISNI:0000 0004 0437 5432) 
11  Burnet Institute, Melbourne, Australia (GRID:grid.1056.2) (ISNI:0000 0001 2224 8486); Monash University, Department of Immunology, Central Clinical School, Melbourne, Australia (GRID:grid.1002.3) (ISNI:0000 0004 1936 7857); The University of Melbourne, Department of Clinical Pathology, Parkville, Australia (GRID:grid.1008.9) (ISNI:0000 0001 2179 088X) 
12  Burnet Institute, Melbourne, Australia (GRID:grid.1056.2) (ISNI:0000 0001 2224 8486); The University of Melbourne, Department of Medicine, Parkville, Australia (GRID:grid.1008.9) (ISNI:0000 0001 2179 088X); Monash University, Department of Microbiology, Central Clinical School, Melbourne, Australia (GRID:grid.1002.3) (ISNI:0000 0004 1936 7857) 
13  University of California San Francisco, San Francisco, USA (GRID:grid.266102.1) (ISNI:0000 0001 2297 6811) 
14  Menzies School of Health Research, Global and Tropical Health Division, Tiwi, Australia (GRID:grid.271089.5) (ISNI:0000 0000 8523 7955); Charles Darwin University, College of Health and Human Sciences, Darwin, Australia (GRID:grid.1043.6) (ISNI:0000 0001 2157 559X) 
15  Burnet Institute, Melbourne, Australia (GRID:grid.1056.2) (ISNI:0000 0001 2224 8486); QIMR-Berghofer Medical Research Institute, Herston, Australia (GRID:grid.1049.c) (ISNI:0000 0001 2294 1395); Menzies School of Health Research, Global and Tropical Health Division, Tiwi, Australia (GRID:grid.271089.5) (ISNI:0000 0000 8523 7955); University of Queensland, Faculty of Medicine, Brisbane, Australia (GRID:grid.1003.2) (ISNI:0000 0000 9320 7537); Griffith University, Brisbane, Australia (GRID:grid.1022.1) (ISNI:0000 0004 0437 5432) 
Publication year
2022
Publication date
2022
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-022-31880-6
ProQuest document ID
2691263625
Copyright
© The Author(s) 2022. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.