title: Dendritic cells derived from BCG-infected precursors induce Th2-like immune response.
abstract: 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.
authors.affiliation: National Institute for Infectious Diseases Lazzaro Spallanzani, IRCCS, Rome, Italy. martino@inmi.it
authors.forename: Angelo
authors.initials: A
authors.lastname: Martino
authors.forename: Alessandra
authors.initials: A
authors.lastname: Sacchi
authors.forename: Nunzia
authors.initials: N
authors.lastname: Sanarico
authors.forename: Francesca
authors.initials: F
authors.lastname: Spadaro
authors.forename: Carlo
authors.initials: C
authors.lastname: Ramoni
authors.forename: Antonio
authors.initials: A
authors.lastname: Ciaramella
authors.forename: Leopoldo Paolo
authors.initials: LP
authors.lastname: Pucillo
authors.forename: Vittorio
authors.initials: V
authors.lastname: Colizzi
authors.forename: Silvia
authors.initials: S
authors.lastname: Vendetti
mesh_terms: 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*
chemical_list: D001500:BCG Vaccine; D016207:Cytokines; D008070:Lipopolysaccharides; D016178:Granulocyte-Macrophage Colony-Stimulating Factor