Staphylococcus aureus-specific TIGIT+ Treg are present in the blood of healthy subjects – a hurdle for vaccination?
Staphylococcus aureus poses an enormous burden of morbidity and mortality worldwide. Making an efficacious vaccine has however proven extremely challenging. Due to colonizing interactions, pre-existing S. aureus-specific CD4+ T cells are often found in the human population and yet a detailed charact...
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| Format: | Article |
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Frontiers Media S.A.
2025-02-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1500696/full |
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| author | Jonah Clegg Jonah Clegg Malgorzata E. Mnich Malgorzata E. Mnich Alberto Carignano Giovanni Cova Simona Tavarini Chiara Sammicheli Bruna Clemente Megan Smith Megan Smith Emilio Siena Monia Bardelli Michela Brazzoli Fabio Bagnoli Rachel M. McLoughlin Elisabetta Soldaini |
| author_facet | Jonah Clegg Jonah Clegg Malgorzata E. Mnich Malgorzata E. Mnich Alberto Carignano Giovanni Cova Simona Tavarini Chiara Sammicheli Bruna Clemente Megan Smith Megan Smith Emilio Siena Monia Bardelli Michela Brazzoli Fabio Bagnoli Rachel M. McLoughlin Elisabetta Soldaini |
| author_sort | Jonah Clegg |
| collection | DOAJ |
| description | Staphylococcus aureus poses an enormous burden of morbidity and mortality worldwide. Making an efficacious vaccine has however proven extremely challenging. Due to colonizing interactions, pre-existing S. aureus-specific CD4+ T cells are often found in the human population and yet a detailed characterization of their phenotypes and how they might in turn impact vaccine efficacy are thus far unknown. Using an activation induced marker assay to sort for S. aureus-specific CD4+ T cells in an effector function-independent manner, single cell transcriptomic analysis was conducted. Remarkably, S. aureus-specific CD4+ T cells consisted not only of a broader spectrum of conventional T cells (Tcon) than previously described but also of regulatory T cells (Treg). As compared to polyclonally-activated CD4+ T cells, S. aureus-specific Tcon were enriched for the expression of the Th17-type cytokine genes IL17A, IL22 and IL26, while higher percentages of S. aureus-specific Treg expressed the T Cell Immunoreceptor with Ig and ITIM domains (TIGIT), a pleiotropic immune checkpoint. Notably, the antagonistic anti-TIGIT mAb Tiragolumab increased IL-1β production in response to S. aureus in vitro. Therefore, these results uncover the presence of S. aureus-specific TIGIT+ Treg in the blood of healthy subjects that could blunt responses to vaccination and indicate TIGIT as a potential targetable biomarker to overcome pre-exposure-induced immunosuppression. |
| format | Article |
| id | doaj-art-08f466c37d57482584a9b0e189fff6dd |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-08f466c37d57482584a9b0e189fff6dd2025-02-06T10:10:23ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-02-011510.3389/fimmu.2024.15006961500696Staphylococcus aureus-specific TIGIT+ Treg are present in the blood of healthy subjects – a hurdle for vaccination?Jonah Clegg0Jonah Clegg1Malgorzata E. Mnich2Malgorzata E. Mnich3Alberto Carignano4Giovanni Cova5Simona Tavarini6Chiara Sammicheli7Bruna Clemente8Megan Smith9Megan Smith10Emilio Siena11Monia Bardelli12Michela Brazzoli13Fabio Bagnoli14Rachel M. McLoughlin15Elisabetta Soldaini16GSK, Research Center, Siena, ItalyHost Pathogen Interactions Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, IrelandGSK, Research Center, Siena, ItalyDepartment of Medical Microbiology, University Medical Center Utrecht, Utrecht, NetherlandsGSK, Research Center, Siena, ItalyGSK, Research Center, Siena, ItalyGSK, Research Center, Siena, ItalyGSK, Research Center, Siena, ItalyGSK, Research Center, Siena, ItalyGSK, Research Center, Siena, ItalyHost Pathogen Interactions Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, IrelandGSK, Research Center, Siena, ItalyGSK, Research Center, Siena, ItalyGSK, Research Center, Siena, ItalyGSK, Research Center, Siena, ItalyHost Pathogen Interactions Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, IrelandGSK, Research Center, Siena, ItalyStaphylococcus aureus poses an enormous burden of morbidity and mortality worldwide. Making an efficacious vaccine has however proven extremely challenging. Due to colonizing interactions, pre-existing S. aureus-specific CD4+ T cells are often found in the human population and yet a detailed characterization of their phenotypes and how they might in turn impact vaccine efficacy are thus far unknown. Using an activation induced marker assay to sort for S. aureus-specific CD4+ T cells in an effector function-independent manner, single cell transcriptomic analysis was conducted. Remarkably, S. aureus-specific CD4+ T cells consisted not only of a broader spectrum of conventional T cells (Tcon) than previously described but also of regulatory T cells (Treg). As compared to polyclonally-activated CD4+ T cells, S. aureus-specific Tcon were enriched for the expression of the Th17-type cytokine genes IL17A, IL22 and IL26, while higher percentages of S. aureus-specific Treg expressed the T Cell Immunoreceptor with Ig and ITIM domains (TIGIT), a pleiotropic immune checkpoint. Notably, the antagonistic anti-TIGIT mAb Tiragolumab increased IL-1β production in response to S. aureus in vitro. Therefore, these results uncover the presence of S. aureus-specific TIGIT+ Treg in the blood of healthy subjects that could blunt responses to vaccination and indicate TIGIT as a potential targetable biomarker to overcome pre-exposure-induced immunosuppression.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1500696/fullStaphylococcus aureusTh17TregTIGIThost-pathogen interactionsvaccines |
| spellingShingle | Jonah Clegg Jonah Clegg Malgorzata E. Mnich Malgorzata E. Mnich Alberto Carignano Giovanni Cova Simona Tavarini Chiara Sammicheli Bruna Clemente Megan Smith Megan Smith Emilio Siena Monia Bardelli Michela Brazzoli Fabio Bagnoli Rachel M. McLoughlin Elisabetta Soldaini Staphylococcus aureus-specific TIGIT+ Treg are present in the blood of healthy subjects – a hurdle for vaccination? Frontiers in Immunology Staphylococcus aureus Th17 Treg TIGIT host-pathogen interactions vaccines |
| title | Staphylococcus aureus-specific TIGIT+ Treg are present in the blood of healthy subjects – a hurdle for vaccination? |
| title_full | Staphylococcus aureus-specific TIGIT+ Treg are present in the blood of healthy subjects – a hurdle for vaccination? |
| title_fullStr | Staphylococcus aureus-specific TIGIT+ Treg are present in the blood of healthy subjects – a hurdle for vaccination? |
| title_full_unstemmed | Staphylococcus aureus-specific TIGIT+ Treg are present in the blood of healthy subjects – a hurdle for vaccination? |
| title_short | Staphylococcus aureus-specific TIGIT+ Treg are present in the blood of healthy subjects – a hurdle for vaccination? |
| title_sort | staphylococcus aureus specific tigit treg are present in the blood of healthy subjects a hurdle for vaccination |
| topic | Staphylococcus aureus Th17 Treg TIGIT host-pathogen interactions vaccines |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1500696/full |
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