title: Bacillus Calmette-Guérin shares with virulent Mycobacterium tuberculosis the capacity to subvert monocyte differentiation into dendritic cell: implication for its efficacy as a vaccine preventing tuberculosis.
abstract: The only available vaccine against tuberculosis (TB) is Bacillus Calmette-Guérin (BCG) whose efficacy in preventing pulmonary tuberculosis is however controversial. Here, we show that BCG infection of monocytes causes their differentiation into mature dendritic cells (DCs) lacking CD1 molecules expression, coupled with suboptimal up-regulation of HLA class II, CD80 and CD40 molecules and a marked unresponsiveness to lipopolysaccharide stimulation. In addition, alloreactive naïve T lymphocytes primed by these subverted DCs did not undergo defined functional polarization, as witnessed by their inability to produce IFN-gamma. Since efficient antigen presentation and IFN-gamma production by mycobacterial-specific T lymphocytes are required for protection against Mycobacterium tuberculosis, our data might provide additional explanation for the low efficacy of BCG vaccination.
authors.affiliation: Dipartimento di Malattie Infettive, Parassitarie e Immunomediate, Istituto Superiore di Sanità, 00161 Rome, Italy.
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Gagliardi
authors.forename: Raffaela
authors.initials: R
authors.lastname: Teloni
authors.forename: Sabrina
authors.initials: S
authors.lastname: Mariotti
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Iona
authors.forename: Manuela
authors.initials: M
authors.lastname: Pardini
authors.forename: Lanfranco
authors.initials: L
authors.lastname: Fattorini
authors.forename: Graziella
authors.initials: G
authors.lastname: Orefici
authors.forename: Roberto
authors.initials: R
authors.lastname: Nisini
mesh_terms: D017951:Antigen Presentation / Q000276:immunology; D018949:Antigens, CD1 / Q000032:analysis; D018122:B7-1 Antigen / Q000032:analysis; D019013:CD40 Antigens / Q000032:analysis; D002454:Cell Differentiation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000382:microbiology*; D006801:Humans; D007371:Interferon-gamma / Q000032:analysis; D016753:Interleukin-10 / Q000032:analysis; D018664:Interleukin-12 / Q000032:analysis; D015850:Interleukin-6 / Q000032:analysis; D008070:Lipopolysaccharides / Q000276:immunology; D008213:Lymphocyte Activation; D009000:Monocytes / Q000276:immunology* / Q000382:microbiology*; D009163:Mycobacterium bovis / Q000276:immunology*; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000472:pathogenicity; D013601:T-Lymphocytes / Q000276:immunology; D014397:Tuberculosis, Pulmonary / Q000517:prevention & control
chemical_list: D018949:Antigens, CD1; D018122:B7-1 Antigen; D019013:CD40 Antigens; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma