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 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.
Department of Immunology and Infectious Biology, Institute of Microbiology, Biotechnology and Immunology, University of Lodz, Banacha Street 12/19, 90-237 Lodz, Poland.
Piotr
P
Szpakowski
UMR1282, Infectiologie et Santé Publique (ISP-311), INRA-Centre Val de Loire, 37380 Nouzilly, France.
Franck
F
Biet
Center for Infection and Immunity of Lille, Institut Pasteur de Lille, 59019 Lille, France ; Inserm U1019, 59019 Lille, France ; CNRS UMR 8204, 59019 Lille, France ; Université Lille Nord de France, 59019 Lille, France.
Camille
C
Locht
Department of Immunology and Infectious Biology, Institute of Microbiology, Biotechnology and Immunology, University of Lodz, Banacha Street 12/19, 90-237 Lodz, Poland.
Małgorzata
M
Paszkiewicz
Department of Immunology and Infectious Biology, Institute of Microbiology, Biotechnology and Immunology, University of Lodz, Banacha Street 12/19, 90-237 Lodz, Poland.
Wiesława
W
Rudnicka
Department of Immunology and Infectious Biology, Institute of Microbiology, Biotechnology and Immunology, University of Lodz, Banacha Street 12/19, 90-237 Lodz, Poland.
Magdalena
M
Druszczyńska
Université Lille Nord de France, 59019 Lille, France ; CNRS-UMR 8576, Unité de Glycobiologie Structurale et Fonctionnelle, IFR 147, Université Lille Nord de France, Université de Lille 1, 59655 Villeneuve d'Ascq, France.
Fabrice
F
Allain
Department of Immunology and Infectious Biology, Institute of Microbiology, Biotechnology and Immunology, University of Lodz, Banacha Street 12/19, 90-237 Lodz, Poland.
Marek
M
Fol
Université Lille Nord de France, 59019 Lille, France ; CNRS-UMR 8576, Unité de Glycobiologie Structurale et Fonctionnelle, IFR 147, Université Lille Nord de France, Université de Lille 1, 59655 Villeneuve d'Ascq, France.
Joël
J
Pestel
Department of Immunology and Infectious Biology, Institute of Microbiology, Biotechnology and Immunology, University of Lodz, Banacha Street 12/19, 90-237 Lodz, Poland.
Magdalena
M
Kowalewicz-Kulbat
D000328:Adult; D001500:BCG Vaccine / Q000276:immunology*; D015415:Biomarkers; D002454:Cell Differentiation; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D005822:Genetic Vectors / Q000235:genetics; D064368:Healthy Volunteers; D006801:Humans; D007156:Immunologic Memory; D016130:Immunophenotyping; D020382:Interleukin-18 / Q000096:biosynthesis*; D008213:Lymphocyte Activation / Q000276:immunology; D009163:Mycobacterium bovis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D014376:Tuberculosis / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control; D014611:Vaccination
D001500:BCG Vaccine; D015415:Biomarkers; D016207:Cytokines; D020382:Interleukin-18