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.
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.
Gagliardi
Maria Cristina
MC
Dipartimento di Malattie Infettive, Parassitarie e Immunomediate, Istituto Superiore di Sanità, 00161 Rome, Italy.
Teloni
Raffaela
R
Mariotti
Sabrina
S
Iona
Elisabetta
E
Pardini
Manuela
M
Fattorini
Lanfranco
L
Orefici
Graziella
G
Nisini
Roberto
R
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
D018949:Antigens, CD1; D018122:B7-1 Antigen; D019013:CD40 Antigens; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma