Journal of Leukocyte Biology Myeloid cells, immune suppression, tumor immunology
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Originally published online as doi:10.1189/jlb.0703313 on July 7, 2004

Published online before print July 7, 2004
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(Journal of Leukocyte Biology. 2004;76:827-834.)
© 2004 by Society for Leukocyte Biology

Dendritic cells derived from BCG-infected precursors induce Th2-like immune response

Angelo Martino*,1, Alessandra Sacchi*, Nunzia Sanarico*,{dagger}, Francesca Spadaro{ddagger}, Carlo Ramoni{ddagger}, Antonio Ciaramella{dagger}, Leopoldo Paolo Pucillo*, Vittorio Colizzi*,{dagger} and Silvia Vendetti*

* National Institute for Infectious Diseases "Lazzaro Spallanzani," IRCCS, Rome, Italy;
{dagger} Department of Biology, Laboratory of Immunopathology and Immunochemistry, University of Rome "Tor Vergata," Italy; and
{ddagger} Laboratory of Cell Biology, Istituto Superiore di Sanità, Rome, Italy

1Correspondence: Laboratory of Immunology and UNESCO Center, Istituto Nazionale Malattie Infettive "L.Spallanzani" Hospital, Via Portuense 292, 00149, Rome, Italy. E-mail: martino{at}inmi.it

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-1ß, 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.

Key Words: mycobacteria • differentiation • CD1a • polarization • cytokines




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