Dendritic Cell Activity Driven by Recombinant Mycobacterium bovis BCG Producing Human IL-18, in Healthy BCG Vaccinated Adults
Tuberculosis remains an enormous global burden, despite wide vaccination coverage with the Bacillus Calmette-Guérin (BCG), the only vaccine available against this disease, indicating that BCG-driven immunity is insufficient to protect the human population against tuberculosis. In this study we const...
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| Format: | Article |
| Language: | English |
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Wiley
2015-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2015/359153 |
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| author | Piotr Szpakowski Franck Biet Camille Locht Małgorzata Paszkiewicz Wiesława Rudnicka Magdalena Druszczyńska Fabrice Allain Marek Fol Joël Pestel Magdalena Kowalewicz-Kulbat |
| author_facet | Piotr Szpakowski Franck Biet Camille Locht Małgorzata Paszkiewicz Wiesława Rudnicka Magdalena Druszczyńska Fabrice Allain Marek Fol Joël Pestel Magdalena Kowalewicz-Kulbat |
| author_sort | Piotr Szpakowski |
| collection | DOAJ |
| description | Tuberculosis remains an enormous global burden, despite wide vaccination coverage with the Bacillus Calmette-Guérin (BCG), the only vaccine available against this disease, indicating that BCG-driven immunity is insufficient to protect the human population against tuberculosis. In this study we constructed recombinant BCG producing human IL-18 (rBCGhIL-18) and investigated whether human IL-18 produced by rBCGhIL-18 modulates DC functions and enhances Th1 responses to mycobacterial antigens in humans. We found that the costimulatory CD86 and CD80 molecules were significantly upregulated on rBCGhIL-18-infected DCs, whereas the stimulation of DCs with nonrecombinant BCG was less effective. In contrast, both BCG strains decreased the DC-SIGN expression on human DCs. The rBCGhIL-18 increased IL-23, IL-10, and IP-10 production by DCs to a greater extent than nonrecombinant BCG. In a coculture system of CD4+ T cells and loaded DCs, rBCGhIL-18 favoured strong IFN-γ but also IL-10 production by naive T cells but not by memory T cells. This was much less the case for nonrecombinant BCG. Thus the expression of IL-18 by recombinant BCG increases IL-23, IP-10, and IL-10 expression by human DCs and enhances their ability to induce IFN-γ and IL-10 expression by naive T cells, without affecting the maturation phenotype of the DCs. |
| format | Article |
| id | doaj-art-6b30fb8becee4beda854a648f0352d59 |
| institution | OA Journals |
| issn | 2314-8861 2314-7156 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-6b30fb8becee4beda854a648f0352d592025-08-20T02:23:59ZengWileyJournal of Immunology Research2314-88612314-71562015-01-01201510.1155/2015/359153359153Dendritic Cell Activity Driven by Recombinant Mycobacterium bovis BCG Producing Human IL-18, in Healthy BCG Vaccinated AdultsPiotr Szpakowski0Franck Biet1Camille Locht2Małgorzata Paszkiewicz3Wiesława Rudnicka4Magdalena Druszczyńska5Fabrice Allain6Marek Fol7Joël Pestel8Magdalena Kowalewicz-Kulbat9Department of Immunology and Infectious Biology, Institute of Microbiology, Biotechnology and Immunology, University of Lodz, Banacha Street 12/19, 90-237 Lodz, PolandUMR1282, Infectiologie et Santé Publique (ISP-311), INRA-Centre Val de Loire, 37380 Nouzilly, FranceCenter for Infection and Immunity of Lille, Institut Pasteur de Lille, 59019 Lille, FranceDepartment of Immunology and Infectious Biology, Institute of Microbiology, Biotechnology and Immunology, University of Lodz, Banacha Street 12/19, 90-237 Lodz, PolandDepartment of Immunology and Infectious Biology, Institute of Microbiology, Biotechnology and Immunology, University of Lodz, Banacha Street 12/19, 90-237 Lodz, PolandDepartment of Immunology and Infectious Biology, Institute of Microbiology, Biotechnology and Immunology, University of Lodz, Banacha Street 12/19, 90-237 Lodz, PolandUniversité Lille Nord de France, 59019 Lille, FranceDepartment of Immunology and Infectious Biology, Institute of Microbiology, Biotechnology and Immunology, University of Lodz, Banacha Street 12/19, 90-237 Lodz, PolandUniversité Lille Nord de France, 59019 Lille, FranceDepartment of Immunology and Infectious Biology, Institute of Microbiology, Biotechnology and Immunology, University of Lodz, Banacha Street 12/19, 90-237 Lodz, PolandTuberculosis remains an enormous global burden, despite wide vaccination coverage with the Bacillus Calmette-Guérin (BCG), the only vaccine available against this disease, indicating that BCG-driven immunity is insufficient to protect the human population against tuberculosis. In this study we constructed recombinant BCG producing human IL-18 (rBCGhIL-18) and investigated whether human IL-18 produced by rBCGhIL-18 modulates DC functions and enhances Th1 responses to mycobacterial antigens in humans. We found that the costimulatory CD86 and CD80 molecules were significantly upregulated on rBCGhIL-18-infected DCs, whereas the stimulation of DCs with nonrecombinant BCG was less effective. In contrast, both BCG strains decreased the DC-SIGN expression on human DCs. The rBCGhIL-18 increased IL-23, IL-10, and IP-10 production by DCs to a greater extent than nonrecombinant BCG. In a coculture system of CD4+ T cells and loaded DCs, rBCGhIL-18 favoured strong IFN-γ but also IL-10 production by naive T cells but not by memory T cells. This was much less the case for nonrecombinant BCG. Thus the expression of IL-18 by recombinant BCG increases IL-23, IP-10, and IL-10 expression by human DCs and enhances their ability to induce IFN-γ and IL-10 expression by naive T cells, without affecting the maturation phenotype of the DCs.http://dx.doi.org/10.1155/2015/359153 |
| spellingShingle | Piotr Szpakowski Franck Biet Camille Locht Małgorzata Paszkiewicz Wiesława Rudnicka Magdalena Druszczyńska Fabrice Allain Marek Fol Joël Pestel Magdalena Kowalewicz-Kulbat Dendritic Cell Activity Driven by Recombinant Mycobacterium bovis BCG Producing Human IL-18, in Healthy BCG Vaccinated Adults Journal of Immunology Research |
| title | Dendritic Cell Activity Driven by Recombinant Mycobacterium bovis BCG Producing Human IL-18, in Healthy BCG Vaccinated Adults |
| title_full | Dendritic Cell Activity Driven by Recombinant Mycobacterium bovis BCG Producing Human IL-18, in Healthy BCG Vaccinated Adults |
| title_fullStr | Dendritic Cell Activity Driven by Recombinant Mycobacterium bovis BCG Producing Human IL-18, in Healthy BCG Vaccinated Adults |
| title_full_unstemmed | Dendritic Cell Activity Driven by Recombinant Mycobacterium bovis BCG Producing Human IL-18, in Healthy BCG Vaccinated Adults |
| title_short | Dendritic Cell Activity Driven by Recombinant Mycobacterium bovis BCG Producing Human IL-18, in Healthy BCG Vaccinated Adults |
| title_sort | dendritic cell activity driven by recombinant mycobacterium bovis bcg producing human il 18 in healthy bcg vaccinated adults |
| url | http://dx.doi.org/10.1155/2015/359153 |
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