The β-NGF/TrkA Signalling Pathway Is Associated With the Production of Anti-Nucleoprotein IgG in Convalescent COVID-19
BackgroundThe presentation of SARS-CoV-2 infection varies from asymptomatic to severe COVID-19. Similarly, high variability in the presence, titre and duration of specific antibodies has been reported. While some host factors determining these differences, such as age and ethnicity have been identif...
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| Format: | Article |
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Frontiers Media S.A.
2022-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.813300/full |
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| author | Carla Usai Joseph M. Gibbons Corinna Pade Wenhao Li Wenhao Li Sabina R. M. Jacobs Áine McKnight Patrick T. F. Kennedy Patrick T. F. Kennedy Upkar S. Gill Upkar S. Gill |
| author_facet | Carla Usai Joseph M. Gibbons Corinna Pade Wenhao Li Wenhao Li Sabina R. M. Jacobs Áine McKnight Patrick T. F. Kennedy Patrick T. F. Kennedy Upkar S. Gill Upkar S. Gill |
| author_sort | Carla Usai |
| collection | DOAJ |
| description | BackgroundThe presentation of SARS-CoV-2 infection varies from asymptomatic to severe COVID-19. Similarly, high variability in the presence, titre and duration of specific antibodies has been reported. While some host factors determining these differences, such as age and ethnicity have been identified, the underlying molecular mechanisms underpinning these differences remain poorly defined.MethodsWe analysed serum and PBMC from 17 subjects with a previous PCR-confirmed SARS-CoV-2 infection and 10 unexposed volunteers following the first wave of the pandemic, in the UK. Anti-NP IgG and neutralising antibodies were measured, as well as a panel of infection and inflammation related cytokines. The virus-specific T cell response was determined by IFN-γ ELISPOT and flow cytometry after overnight incubation of PBMCs with pools of selected SARS-CoV-2 specific peptides.ResultsSeven of 17 convalescent subjects had undetectable levels of anti-NP IgG, and a positive correlation was shown between anti-NP IgG levels and the titre of neutralising antibodies (IC50). In contrast, a discrepancy was noted between antibody levels and T cell IFN-γ production by ELISpot following stimulation with specific peptides. Among the analysed cytokines, β-NGF and IL-1α levels were significantly different between anti-NP positive and negative subjects, and only β-NGF significantly correlated with anti-NP positivity. Interestingly, CD4+ T cells of anti-NP negative subjects expressed lower amounts of the β-NGF-specific receptor TrkA.ConclusionsOur results suggest that the β-NGF/TrkA signalling pathway is associated with the production of anti-NP specific antibody in mild SARS-CoV-2 infection and the mechanistic regulation of this pathway in COVID-19 requires further investigation. |
| first_indexed | 2024-12-20T13:29:11Z |
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| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-20T13:29:11Z |
| publishDate | 2022-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-ba889035419841beb5f4fb551228df612022-12-21T19:39:09ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-01-011210.3389/fimmu.2021.813300813300The β-NGF/TrkA Signalling Pathway Is Associated With the Production of Anti-Nucleoprotein IgG in Convalescent COVID-19Carla Usai0Joseph M. Gibbons1Corinna Pade2Wenhao Li3Wenhao Li4Sabina R. M. Jacobs5Áine McKnight6Patrick T. F. Kennedy7Patrick T. F. Kennedy8Upkar S. Gill9Upkar S. Gill10Centre for Immunobiology, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United KingdomCentre for Immunobiology, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United KingdomCentre for Immunobiology, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United KingdomCentre for Immunobiology, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United KingdomBarts Health National Health Service (NHS) Trust, The Royal London Hospital, London, United KingdomCentre for Immunobiology, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United KingdomCentre for Immunobiology, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United KingdomCentre for Immunobiology, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United KingdomBarts Health National Health Service (NHS) Trust, The Royal London Hospital, London, United KingdomCentre for Immunobiology, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United KingdomBarts Health National Health Service (NHS) Trust, The Royal London Hospital, London, United KingdomBackgroundThe presentation of SARS-CoV-2 infection varies from asymptomatic to severe COVID-19. Similarly, high variability in the presence, titre and duration of specific antibodies has been reported. While some host factors determining these differences, such as age and ethnicity have been identified, the underlying molecular mechanisms underpinning these differences remain poorly defined.MethodsWe analysed serum and PBMC from 17 subjects with a previous PCR-confirmed SARS-CoV-2 infection and 10 unexposed volunteers following the first wave of the pandemic, in the UK. Anti-NP IgG and neutralising antibodies were measured, as well as a panel of infection and inflammation related cytokines. The virus-specific T cell response was determined by IFN-γ ELISPOT and flow cytometry after overnight incubation of PBMCs with pools of selected SARS-CoV-2 specific peptides.ResultsSeven of 17 convalescent subjects had undetectable levels of anti-NP IgG, and a positive correlation was shown between anti-NP IgG levels and the titre of neutralising antibodies (IC50). In contrast, a discrepancy was noted between antibody levels and T cell IFN-γ production by ELISpot following stimulation with specific peptides. Among the analysed cytokines, β-NGF and IL-1α levels were significantly different between anti-NP positive and negative subjects, and only β-NGF significantly correlated with anti-NP positivity. Interestingly, CD4+ T cells of anti-NP negative subjects expressed lower amounts of the β-NGF-specific receptor TrkA.ConclusionsOur results suggest that the β-NGF/TrkA signalling pathway is associated with the production of anti-NP specific antibody in mild SARS-CoV-2 infection and the mechanistic regulation of this pathway in COVID-19 requires further investigation.https://www.frontiersin.org/articles/10.3389/fimmu.2021.813300/fullCOVID-19antibody productionβ-NGFT cellsSARS-CoV-2 |
| spellingShingle | Carla Usai Joseph M. Gibbons Corinna Pade Wenhao Li Wenhao Li Sabina R. M. Jacobs Áine McKnight Patrick T. F. Kennedy Patrick T. F. Kennedy Upkar S. Gill Upkar S. Gill The β-NGF/TrkA Signalling Pathway Is Associated With the Production of Anti-Nucleoprotein IgG in Convalescent COVID-19 Frontiers in Immunology COVID-19 antibody production β-NGF T cells SARS-CoV-2 |
| title | The β-NGF/TrkA Signalling Pathway Is Associated With the Production of Anti-Nucleoprotein IgG in Convalescent COVID-19 |
| title_full | The β-NGF/TrkA Signalling Pathway Is Associated With the Production of Anti-Nucleoprotein IgG in Convalescent COVID-19 |
| title_fullStr | The β-NGF/TrkA Signalling Pathway Is Associated With the Production of Anti-Nucleoprotein IgG in Convalescent COVID-19 |
| title_full_unstemmed | The β-NGF/TrkA Signalling Pathway Is Associated With the Production of Anti-Nucleoprotein IgG in Convalescent COVID-19 |
| title_short | The β-NGF/TrkA Signalling Pathway Is Associated With the Production of Anti-Nucleoprotein IgG in Convalescent COVID-19 |
| title_sort | β ngf trka signalling pathway is associated with the production of anti nucleoprotein igg in convalescent covid 19 |
| topic | COVID-19 antibody production β-NGF T cells SARS-CoV-2 |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.813300/full |
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