Lipidation of pneumococcal proteins enables activation of human antigen-presenting cells and initiation of an adaptive immune response
Streptococcus pneumoniae remains a significant global threat, with existing vaccines having important limitations such as restricted serotype coverage and high manufacturing costs. Pneumococcal lipoproteins are emerging as promising vaccine candidates due to their surface exposure and conservation a...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2024-04-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1392316/full |
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| author | Antje D. Paulikat Dominik Schwudke Dominik Schwudke Dominik Schwudke Sven Hammerschmidt Franziska Voß |
| author_facet | Antje D. Paulikat Dominik Schwudke Dominik Schwudke Dominik Schwudke Sven Hammerschmidt Franziska Voß |
| author_sort | Antje D. Paulikat |
| collection | DOAJ |
| description | Streptococcus pneumoniae remains a significant global threat, with existing vaccines having important limitations such as restricted serotype coverage and high manufacturing costs. Pneumococcal lipoproteins are emerging as promising vaccine candidates due to their surface exposure and conservation across various serotypes. While prior studies have explored their potential in mice, data in a human context and insights into the impact of the lipid moiety remain limited. In the present study, we examined the immunogenicity of two pneumococcal lipoproteins, DacB and MetQ, both in lipidated and non-lipidated versions, by stimulation of primary human immune cells. Immune responses were assessed by the expression of common surface markers for activation and maturation as well as cytokines released into the supernatant. Our findings indicate that in the case of MetQ lipidation was crucial for activation of human antigen-presenting cells such as dendritic cells and macrophages, while non-lipidated DacB demonstrated an intrinsic potential to induce an innate immune response. Nevertheless, immune responses to both proteins were enhanced by lipidation. Interestingly, following stimulation of dendritic cells with DacB, LipDacB and LipMetQ, cytokine levels of IL-6 and IL-23 were significantly increased, which are implicated in triggering potentially important Th17 cell responses. Furthermore, LipDacB and LipMetQ were able to induce proliferation of CD4+ T cells indicating their potential to induce an adaptive immune response. These findings contribute valuable insights into the immunogenic properties of pneumococcal lipoproteins, emphasizing their potential role in vaccine development against pneumococcal infections. |
| first_indexed | 2024-04-24T07:04:41Z |
| format | Article |
| id | doaj.art-c85ee291149641538c48408d52ca3cd9 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-24T07:04:41Z |
| publishDate | 2024-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-c85ee291149641538c48408d52ca3cd92024-04-22T04:37:44ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-04-011510.3389/fimmu.2024.13923161392316Lipidation of pneumococcal proteins enables activation of human antigen-presenting cells and initiation of an adaptive immune responseAntje D. Paulikat0Dominik Schwudke1Dominik Schwudke2Dominik Schwudke3Sven Hammerschmidt4Franziska Voß5Department of Molecular Genetics and Infection Biology, Interfaculty Institute of Genetics and Functional Genomics, Center for Functional Genomics of Microbes, University of Greifswald, Greifswald, GermanyDivision of Bioanalytical Chemistry, Research Center Borstel - Leibniz Lung Center, Borstel, GermanyGerman Center for Infection Research, Thematic Translational Unit Tuberculosis, Partner Site Hamburg-Lübeck-Borstel-Riems, Borstel, GermanyGerman Center for Lung Research (DZL), Airway Research Center North (ARCN), Research Center Borstel, Leibniz Lung Center, Borstel, GermanyDepartment of Molecular Genetics and Infection Biology, Interfaculty Institute of Genetics and Functional Genomics, Center for Functional Genomics of Microbes, University of Greifswald, Greifswald, GermanyDepartment of Molecular Genetics and Infection Biology, Interfaculty Institute of Genetics and Functional Genomics, Center for Functional Genomics of Microbes, University of Greifswald, Greifswald, GermanyStreptococcus pneumoniae remains a significant global threat, with existing vaccines having important limitations such as restricted serotype coverage and high manufacturing costs. Pneumococcal lipoproteins are emerging as promising vaccine candidates due to their surface exposure and conservation across various serotypes. While prior studies have explored their potential in mice, data in a human context and insights into the impact of the lipid moiety remain limited. In the present study, we examined the immunogenicity of two pneumococcal lipoproteins, DacB and MetQ, both in lipidated and non-lipidated versions, by stimulation of primary human immune cells. Immune responses were assessed by the expression of common surface markers for activation and maturation as well as cytokines released into the supernatant. Our findings indicate that in the case of MetQ lipidation was crucial for activation of human antigen-presenting cells such as dendritic cells and macrophages, while non-lipidated DacB demonstrated an intrinsic potential to induce an innate immune response. Nevertheless, immune responses to both proteins were enhanced by lipidation. Interestingly, following stimulation of dendritic cells with DacB, LipDacB and LipMetQ, cytokine levels of IL-6 and IL-23 were significantly increased, which are implicated in triggering potentially important Th17 cell responses. Furthermore, LipDacB and LipMetQ were able to induce proliferation of CD4+ T cells indicating their potential to induce an adaptive immune response. These findings contribute valuable insights into the immunogenic properties of pneumococcal lipoproteins, emphasizing their potential role in vaccine development against pneumococcal infections.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1392316/fullStreptococcus pneumoniaelipoproteinslipidationimmune responsevaccineantigen presenting cells |
| spellingShingle | Antje D. Paulikat Dominik Schwudke Dominik Schwudke Dominik Schwudke Sven Hammerschmidt Franziska Voß Lipidation of pneumococcal proteins enables activation of human antigen-presenting cells and initiation of an adaptive immune response Frontiers in Immunology Streptococcus pneumoniae lipoproteins lipidation immune response vaccine antigen presenting cells |
| title | Lipidation of pneumococcal proteins enables activation of human antigen-presenting cells and initiation of an adaptive immune response |
| title_full | Lipidation of pneumococcal proteins enables activation of human antigen-presenting cells and initiation of an adaptive immune response |
| title_fullStr | Lipidation of pneumococcal proteins enables activation of human antigen-presenting cells and initiation of an adaptive immune response |
| title_full_unstemmed | Lipidation of pneumococcal proteins enables activation of human antigen-presenting cells and initiation of an adaptive immune response |
| title_short | Lipidation of pneumococcal proteins enables activation of human antigen-presenting cells and initiation of an adaptive immune response |
| title_sort | lipidation of pneumococcal proteins enables activation of human antigen presenting cells and initiation of an adaptive immune response |
| topic | Streptococcus pneumoniae lipoproteins lipidation immune response vaccine antigen presenting cells |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1392316/full |
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