Targeting Mycobacterium tuberculosis Antigens to Dendritic Cells via the DC-Specific-ICAM3-Grabbing-Nonintegrin Receptor Induces Strong T-Helper 1 Immune Responses
Tuberculosis remains a major global health problem and efforts to develop a more effective vaccine have been unsuccessful so far. Targeting antigens (Ags) to dendritic cells (DCs) in vivo has emerged as a new promising vaccine strategy. In this approach, Ags are delivered directly to DCs via antibod...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-03-01
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| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/article/10.3389/fimmu.2018.00471/full |
| _version_ | 1817981085086121984 |
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| author | Lis Noelia Velasquez Philipp Stüve Maria Virginia Gentilini Maxine Swallow Judith Bartel Nils Yngve Lycke Daniel Barkan Mariana Martina Hugo D. Lujan Hakan Kalay Yvette van Kooyk Tim D. Sparwasser Luciana Berod |
| author_facet | Lis Noelia Velasquez Philipp Stüve Maria Virginia Gentilini Maxine Swallow Judith Bartel Nils Yngve Lycke Daniel Barkan Mariana Martina Hugo D. Lujan Hakan Kalay Yvette van Kooyk Tim D. Sparwasser Luciana Berod |
| author_sort | Lis Noelia Velasquez |
| collection | DOAJ |
| description | Tuberculosis remains a major global health problem and efforts to develop a more effective vaccine have been unsuccessful so far. Targeting antigens (Ags) to dendritic cells (DCs) in vivo has emerged as a new promising vaccine strategy. In this approach, Ags are delivered directly to DCs via antibodies that bind to endocytic cell-surface receptors. Here, we explored DC-specific-ICAM3-grabbing-nonintegrin (DC-SIGN) targeting as a potential vaccine against tuberculosis. For this, we made use of the hSIGN mouse model that expresses human DC-SIGN under the control of the murine CD11c promoter. We show that in vitro and in vivo delivery of anti-DC-SIGN antibodies conjugated to Ag85B and peptide 25 of Ag85B in combination with anti-CD40, the fungal cell wall component zymosan, and the cholera toxin-derived fusion protein CTA1-DD induces strong Ag-specific CD4+ T-cell responses. Improved anti-mycobacterial immunity was accompanied by increased frequencies of Ag-specific IFN-γ+ IL-2+ TNF-α+ polyfunctional CD4+ T cells in vaccinated mice compared with controls. Taken together, in this study we provide the proof of concept that the human DC-SIGN receptor can be efficiently exploited for vaccine purposes to promote immunity against mycobacterial infections. |
| first_indexed | 2024-04-13T23:02:22Z |
| format | Article |
| id | doaj.art-e705f8d8f4c2409594cf503f70e2de20 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-13T23:02:22Z |
| publishDate | 2018-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-e705f8d8f4c2409594cf503f70e2de202022-12-22T02:25:49ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-03-01910.3389/fimmu.2018.00471338374Targeting Mycobacterium tuberculosis Antigens to Dendritic Cells via the DC-Specific-ICAM3-Grabbing-Nonintegrin Receptor Induces Strong T-Helper 1 Immune ResponsesLis Noelia Velasquez0Philipp Stüve1Maria Virginia Gentilini2Maxine Swallow3Judith Bartel4Nils Yngve Lycke5Daniel Barkan6Mariana Martina7Hugo D. Lujan8Hakan Kalay9Yvette van Kooyk10Tim D. Sparwasser11Luciana Berod12Institute of Infection Immunology, TWINCORE, Centre for Experimental and Clinical Infection Research, A Joint Venture between the Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI), Hannover, GermanyInstitute of Infection Immunology, TWINCORE, Centre for Experimental and Clinical Infection Research, A Joint Venture between the Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI), Hannover, GermanyInstitute of Infection Immunology, TWINCORE, Centre for Experimental and Clinical Infection Research, A Joint Venture between the Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI), Hannover, GermanyInstitute of Infection Immunology, TWINCORE, Centre for Experimental and Clinical Infection Research, A Joint Venture between the Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI), Hannover, GermanyInstitute of Infection Immunology, TWINCORE, Centre for Experimental and Clinical Infection Research, A Joint Venture between the Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI), Hannover, GermanyMucosal Immunobiology and Vaccine Center (MIVAC), Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, Gothenburg, SwedenKoret School of Veterinary Medicine, Robert H. Smith Faculty of Agriculture, Food and Environment, Hebrew University of Jerusalem, Rehovot, IsraelLaboratory of Biochemistry and Molecular Biology, School of Medicine, Catholic University of Córdoba, Córdoba, ArgentinaLaboratory of Biochemistry and Molecular Biology, School of Medicine, Catholic University of Córdoba, Córdoba, ArgentinaDepartment of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, NetherlandsDepartment of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, NetherlandsInstitute of Infection Immunology, TWINCORE, Centre for Experimental and Clinical Infection Research, A Joint Venture between the Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI), Hannover, GermanyInstitute of Infection Immunology, TWINCORE, Centre for Experimental and Clinical Infection Research, A Joint Venture between the Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI), Hannover, GermanyTuberculosis remains a major global health problem and efforts to develop a more effective vaccine have been unsuccessful so far. Targeting antigens (Ags) to dendritic cells (DCs) in vivo has emerged as a new promising vaccine strategy. In this approach, Ags are delivered directly to DCs via antibodies that bind to endocytic cell-surface receptors. Here, we explored DC-specific-ICAM3-grabbing-nonintegrin (DC-SIGN) targeting as a potential vaccine against tuberculosis. For this, we made use of the hSIGN mouse model that expresses human DC-SIGN under the control of the murine CD11c promoter. We show that in vitro and in vivo delivery of anti-DC-SIGN antibodies conjugated to Ag85B and peptide 25 of Ag85B in combination with anti-CD40, the fungal cell wall component zymosan, and the cholera toxin-derived fusion protein CTA1-DD induces strong Ag-specific CD4+ T-cell responses. Improved anti-mycobacterial immunity was accompanied by increased frequencies of Ag-specific IFN-γ+ IL-2+ TNF-α+ polyfunctional CD4+ T cells in vaccinated mice compared with controls. Taken together, in this study we provide the proof of concept that the human DC-SIGN receptor can be efficiently exploited for vaccine purposes to promote immunity against mycobacterial infections.http://journal.frontiersin.org/article/10.3389/fimmu.2018.00471/fullDC-specific-ICAM3-grabbing-nonintegrintuberculosisvaccinedendritic cellsAg85B |
| spellingShingle | Lis Noelia Velasquez Philipp Stüve Maria Virginia Gentilini Maxine Swallow Judith Bartel Nils Yngve Lycke Daniel Barkan Mariana Martina Hugo D. Lujan Hakan Kalay Yvette van Kooyk Tim D. Sparwasser Luciana Berod Targeting Mycobacterium tuberculosis Antigens to Dendritic Cells via the DC-Specific-ICAM3-Grabbing-Nonintegrin Receptor Induces Strong T-Helper 1 Immune Responses Frontiers in Immunology DC-specific-ICAM3-grabbing-nonintegrin tuberculosis vaccine dendritic cells Ag85B |
| title | Targeting Mycobacterium tuberculosis Antigens to Dendritic Cells via the DC-Specific-ICAM3-Grabbing-Nonintegrin Receptor Induces Strong T-Helper 1 Immune Responses |
| title_full | Targeting Mycobacterium tuberculosis Antigens to Dendritic Cells via the DC-Specific-ICAM3-Grabbing-Nonintegrin Receptor Induces Strong T-Helper 1 Immune Responses |
| title_fullStr | Targeting Mycobacterium tuberculosis Antigens to Dendritic Cells via the DC-Specific-ICAM3-Grabbing-Nonintegrin Receptor Induces Strong T-Helper 1 Immune Responses |
| title_full_unstemmed | Targeting Mycobacterium tuberculosis Antigens to Dendritic Cells via the DC-Specific-ICAM3-Grabbing-Nonintegrin Receptor Induces Strong T-Helper 1 Immune Responses |
| title_short | Targeting Mycobacterium tuberculosis Antigens to Dendritic Cells via the DC-Specific-ICAM3-Grabbing-Nonintegrin Receptor Induces Strong T-Helper 1 Immune Responses |
| title_sort | targeting mycobacterium tuberculosis antigens to dendritic cells via the dc specific icam3 grabbing nonintegrin receptor induces strong t helper 1 immune responses |
| topic | DC-specific-ICAM3-grabbing-nonintegrin tuberculosis vaccine dendritic cells Ag85B |
| url | http://journal.frontiersin.org/article/10.3389/fimmu.2018.00471/full |
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