Dendritic cells derived from BCG-infected precursors induce Th2-like immune response.
Human monocytes can differentiate into dendritic cells (DCs) according to the nature of environmental signals. We tested here whether the infection with the live tuberculosis vaccine bacillus Calmette-Guerin (BCG), which is known to be limited in preventing pulmonary tuberculosis, modulates monocyte and DC differentiation. We found that monocytes infected with BCG differentiate into CD1a- DCs (BCG-DCs) in the presence of granulocyte macrophage-colony stimulating factor and interleukin (IL)-4 and acquired a mature phenotype in the absence of maturation stimuli. In addition, BCG-DCs produced proinflammatory cytokines (tumor necrosis factor alpha, IL-1beta, IL-6) and IL-10 but not IL-12. BCG-DCs were able to stimulate allogeneic T lymphocytes to a similar degree as DCs generated in the absence of infection. However, BCG-DCs induced IL-4 production when cocultured with human cord-blood mononuclear cells. The induction of IL-4 production by DCs generated by BCG-infected monocytes could explain the failure of the BCG vaccine to prevent pulmonary tuberculosis.
Martino
Angelo
A
National Institute for Infectious Diseases Lazzaro Spallanzani, IRCCS, Rome, Italy. martino@inmi.it
Sacchi
Alessandra
A
Sanarico
Nunzia
N
Spadaro
Francesca
F
Ramoni
Carlo
C
Ciaramella
Antonio
A
Pucillo
Leopoldo Paolo
LP
Colizzi
Vittorio
V
Vendetti
Silvia
S
D001500:BCG Vaccine / Q000276:immunology*; D002454:Cell Differentiation; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D005312:Fetal Blood; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000382:microbiology*; D009163:Mycobacterium bovis / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
D001500:BCG Vaccine; D016207:Cytokines; D008070:Lipopolysaccharides; D016178:Granulocyte-Macrophage Colony-Stimulating Factor