Adults with Plasmodium falciparum malaria have higher magnitude and quality of circulating T-follicular helper cells compared to children
Summary: Background: Protective malarial antibodies are acquired more rapidly in adults than children, independently of cumulative exposure, however the cellular responses mediating these differences are unknown. CD4 T-follicular helper (Tfh) cells have key roles in inducing antibodies, with Th2-Tf...
| Main Authors: | , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2022-01-01
|
| Series: | EBioMedicine |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396421005788 |
| _version_ | 1818369510992773120 |
|---|---|
| author | Damian. A. Oyong Jessica. R. Loughland Megan. S.F. Soon Jo-Anne Chan Dean Andrew Bruce D. Wines P. Mark Hogarth Stuart D. Olver Alika D. Collinge Antiopi Varelias James G. Beeson Enny Kenangalem Ric N. Price Nicholas M. Anstey Gabriela Minigo Michelle J. Boyle |
| author_facet | Damian. A. Oyong Jessica. R. Loughland Megan. S.F. Soon Jo-Anne Chan Dean Andrew Bruce D. Wines P. Mark Hogarth Stuart D. Olver Alika D. Collinge Antiopi Varelias James G. Beeson Enny Kenangalem Ric N. Price Nicholas M. Anstey Gabriela Minigo Michelle J. Boyle |
| author_sort | Damian. A. Oyong |
| collection | DOAJ |
| description | Summary: Background: Protective malarial antibodies are acquired more rapidly in adults than children, independently of cumulative exposure, however the cellular responses mediating these differences are unknown. CD4 T-follicular helper (Tfh) cells have key roles in inducing antibodies, with Th2-Tfh cell activation associated with antibody development in malaria. Whether Tfh cell activation in malaria is age dependent is unknown and no studies have compared Tfh cell activation in children and adults with malaria. Methods: We undertook a comprehensive study of Tfh cells, along with B cells and antibody induction in children and adults with malaria. Activation and proliferation of circulating Tfh (cTfh) cell subsets was measured ex vivo and parasite-specific Tfh cell frequencies and functions studied with Activation Induced Marker (AIM) assays and intracellular cytokine staining. Findings: During acute malaria, the magnitude of cTfh cell activation was higher in adults than in children and occurred across all cTfh cell subsets in adults but was restricted only to the Th1-cTfh subset in children. Further, adults had higher levels of parasite-specific cTfh cells, and cTfh cells which produced more Th2-Tfh associated cytokine IL-4. Consistent with a role of higher Tfh cell activation in rapid immune development in adults, adults had higher activation of B cells during infection and higher induction of antibodies 7 and 28 days after malaria compared to children. Interpretation: Our data provide evidence that age impacts Tfh cell activation during malaria, and that these differences may influence antibody induction after treatment. Findings have important implications for vaccine development in children. Funding: This word was supported by the National Health and Medical Research Council of Australia, Wellcome Trust, Charles Darwin University Menzies School of Health Research, Channel 7 Children's Research Foundation, and National Health Institute. |
| first_indexed | 2024-12-13T23:25:00Z |
| format | Article |
| id | doaj.art-5dad9189a89a42f9808a70848568eb43 |
| institution | Directory Open Access Journal |
| issn | 2352-3964 |
| language | English |
| last_indexed | 2024-12-13T23:25:00Z |
| publishDate | 2022-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj.art-5dad9189a89a42f9808a70848568eb432022-12-21T23:27:34ZengElsevierEBioMedicine2352-39642022-01-0175103784Adults with Plasmodium falciparum malaria have higher magnitude and quality of circulating T-follicular helper cells compared to childrenDamian. A. Oyong0Jessica. R. Loughland1Megan. S.F. Soon2Jo-Anne Chan3Dean Andrew4Bruce D. Wines5P. Mark Hogarth6Stuart D. Olver7Alika D. Collinge8Antiopi Varelias9James G. Beeson10Enny Kenangalem11Ric N. Price12Nicholas M. Anstey13Gabriela Minigo14Michelle J. Boyle15Global and Tropical Health Division, Menzies School of Health Research, Darwin, Northern Territory, Australia; Charles Darwin University, Darwin, NT, AustraliaGlobal and Tropical Health Division, Menzies School of Health Research, Darwin, Northern Territory, Australia; QIMR Berghofer Medical Research Institute, Brisbane, QLD, AustraliaQIMR Berghofer Medical Research Institute, Brisbane, QLD, AustraliaBurnet Institute, Melbourne, VIC, Australia; Department of Immunology, Central Clinical School, Monash University, VIC, Australia; Department of Medicine, University of Melbourne, VIC, AustraliaQIMR Berghofer Medical Research Institute, Brisbane, QLD, AustraliaBurnet Institute, Melbourne, VIC, Australia; Department of Immunology, Central Clinical School, Monash University, VIC, Australia; Department of Clinical Pathology, University of Melbourne, VIC, AustraliaBurnet Institute, Melbourne, VIC, Australia; Department of Immunology, Central Clinical School, Monash University, VIC, Australia; Department of Clinical Pathology, University of Melbourne, VIC, AustraliaQIMR Berghofer Medical Research Institute, Brisbane, QLD, AustraliaQIMR Berghofer Medical Research Institute, Brisbane, QLD, AustraliaQIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia; Faculty of Medicine, The University of Queensland, QLD, AustraliaBurnet Institute, Melbourne, VIC, Australia; Department of Medicine, University of Melbourne, VIC, Australia; Department of Microbiology, Monash University, VIC, AustraliaTimika Malaria Research Program, Papuan Health and Community Development Foundation, Timika, Papua, Indonesia; District Health Authority, Timika, Papua, IndonesiaGlobal and Tropical Health Division, Menzies School of Health Research, Darwin, Northern Territory, Australia; Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK; Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, ThailandGlobal and Tropical Health Division, Menzies School of Health Research, Darwin, Northern Territory, AustraliaGlobal and Tropical Health Division, Menzies School of Health Research, Darwin, Northern Territory, Australia; Charles Darwin University, Darwin, NT, AustraliaGlobal and Tropical Health Division, Menzies School of Health Research, Darwin, Northern Territory, Australia; QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia; Burnet Institute, Melbourne, VIC, Australia; Faculty of Medicine, The University of Queensland, QLD, Australia; Corresponding author. Human Malaria Immunology Group, QIMR Berghofer, 300 Herston Rd, 4006 Brisbane City, QLD, Australia. Phone: +61 7 3845 3726Summary: Background: Protective malarial antibodies are acquired more rapidly in adults than children, independently of cumulative exposure, however the cellular responses mediating these differences are unknown. CD4 T-follicular helper (Tfh) cells have key roles in inducing antibodies, with Th2-Tfh cell activation associated with antibody development in malaria. Whether Tfh cell activation in malaria is age dependent is unknown and no studies have compared Tfh cell activation in children and adults with malaria. Methods: We undertook a comprehensive study of Tfh cells, along with B cells and antibody induction in children and adults with malaria. Activation and proliferation of circulating Tfh (cTfh) cell subsets was measured ex vivo and parasite-specific Tfh cell frequencies and functions studied with Activation Induced Marker (AIM) assays and intracellular cytokine staining. Findings: During acute malaria, the magnitude of cTfh cell activation was higher in adults than in children and occurred across all cTfh cell subsets in adults but was restricted only to the Th1-cTfh subset in children. Further, adults had higher levels of parasite-specific cTfh cells, and cTfh cells which produced more Th2-Tfh associated cytokine IL-4. Consistent with a role of higher Tfh cell activation in rapid immune development in adults, adults had higher activation of B cells during infection and higher induction of antibodies 7 and 28 days after malaria compared to children. Interpretation: Our data provide evidence that age impacts Tfh cell activation during malaria, and that these differences may influence antibody induction after treatment. Findings have important implications for vaccine development in children. Funding: This word was supported by the National Health and Medical Research Council of Australia, Wellcome Trust, Charles Darwin University Menzies School of Health Research, Channel 7 Children's Research Foundation, and National Health Institute.http://www.sciencedirect.com/science/article/pii/S2352396421005788Plasmodium falciparumT-follicular helper cellsimmunitymalariaantibodies |
| spellingShingle | Damian. A. Oyong Jessica. R. Loughland Megan. S.F. Soon Jo-Anne Chan Dean Andrew Bruce D. Wines P. Mark Hogarth Stuart D. Olver Alika D. Collinge Antiopi Varelias James G. Beeson Enny Kenangalem Ric N. Price Nicholas M. Anstey Gabriela Minigo Michelle J. Boyle Adults with Plasmodium falciparum malaria have higher magnitude and quality of circulating T-follicular helper cells compared to children EBioMedicine Plasmodium falciparum T-follicular helper cells immunity malaria antibodies |
| title | Adults with Plasmodium falciparum malaria have higher magnitude and quality of circulating T-follicular helper cells compared to children |
| title_full | Adults with Plasmodium falciparum malaria have higher magnitude and quality of circulating T-follicular helper cells compared to children |
| title_fullStr | Adults with Plasmodium falciparum malaria have higher magnitude and quality of circulating T-follicular helper cells compared to children |
| title_full_unstemmed | Adults with Plasmodium falciparum malaria have higher magnitude and quality of circulating T-follicular helper cells compared to children |
| title_short | Adults with Plasmodium falciparum malaria have higher magnitude and quality of circulating T-follicular helper cells compared to children |
| title_sort | adults with plasmodium falciparum malaria have higher magnitude and quality of circulating t follicular helper cells compared to children |
| topic | Plasmodium falciparum T-follicular helper cells immunity malaria antibodies |
| url | http://www.sciencedirect.com/science/article/pii/S2352396421005788 |
| work_keys_str_mv | AT damianaoyong adultswithplasmodiumfalciparummalariahavehighermagnitudeandqualityofcirculatingtfollicularhelpercellscomparedtochildren AT jessicarloughland adultswithplasmodiumfalciparummalariahavehighermagnitudeandqualityofcirculatingtfollicularhelpercellscomparedtochildren AT megansfsoon adultswithplasmodiumfalciparummalariahavehighermagnitudeandqualityofcirculatingtfollicularhelpercellscomparedtochildren AT joannechan adultswithplasmodiumfalciparummalariahavehighermagnitudeandqualityofcirculatingtfollicularhelpercellscomparedtochildren AT deanandrew adultswithplasmodiumfalciparummalariahavehighermagnitudeandqualityofcirculatingtfollicularhelpercellscomparedtochildren AT brucedwines adultswithplasmodiumfalciparummalariahavehighermagnitudeandqualityofcirculatingtfollicularhelpercellscomparedtochildren AT pmarkhogarth adultswithplasmodiumfalciparummalariahavehighermagnitudeandqualityofcirculatingtfollicularhelpercellscomparedtochildren AT stuartdolver adultswithplasmodiumfalciparummalariahavehighermagnitudeandqualityofcirculatingtfollicularhelpercellscomparedtochildren AT alikadcollinge adultswithplasmodiumfalciparummalariahavehighermagnitudeandqualityofcirculatingtfollicularhelpercellscomparedtochildren AT antiopivarelias adultswithplasmodiumfalciparummalariahavehighermagnitudeandqualityofcirculatingtfollicularhelpercellscomparedtochildren AT jamesgbeeson adultswithplasmodiumfalciparummalariahavehighermagnitudeandqualityofcirculatingtfollicularhelpercellscomparedtochildren AT ennykenangalem adultswithplasmodiumfalciparummalariahavehighermagnitudeandqualityofcirculatingtfollicularhelpercellscomparedtochildren AT ricnprice adultswithplasmodiumfalciparummalariahavehighermagnitudeandqualityofcirculatingtfollicularhelpercellscomparedtochildren AT nicholasmanstey adultswithplasmodiumfalciparummalariahavehighermagnitudeandqualityofcirculatingtfollicularhelpercellscomparedtochildren AT gabrielaminigo adultswithplasmodiumfalciparummalariahavehighermagnitudeandqualityofcirculatingtfollicularhelpercellscomparedtochildren AT michellejboyle adultswithplasmodiumfalciparummalariahavehighermagnitudeandqualityofcirculatingtfollicularhelpercellscomparedtochildren |