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Published online before print October 26, 2007
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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0707457


Received for publication July 12, 2007.
Revised September 12, 2007.
Accepted for publication October 5, 2007.


Article

Streptococcus pyogenes activates human plasmacytoid and myeloid dendritic cells

Ville Veckman @ and Ilkka Julkunen

Department of Viral Diseases and Immunology, National Public Health Institute, Helsinki, Finland

@ To whom correspondence should be addressed. E-mail: ville.veckman{at}ktl.fi.


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Abstract

Human peripheral blood contains two major dendritic cell (DC) populations, namely CD11cCD123+ plasmacytoid DCs (PDCs) and CD11c+CD123 myeloid DCs (MDCs). Although the activation of these DC types by various TLR ligands has been relatively well-characterized, less is known about the ability of whole live bacteria to induce PDC and MDC activation. In the present report, we have compared the activation of human PDCs and MDCs in response to major human bacterial pathogen Streptococcus pyogenes (group A streptococci) and influenza A virus. S. pyogenes stimulation resulted in the maturation of both DC types, as evidenced by enhanced expression of costimulatory molecules and production of proinflammatory cytokines and chemokines. Furthermore, S. pyogenes-stimulated PDCs and MDCs activated naïve CD4+ T cells and enhanced their Th1 cytokine production. Influenza A virus infection induced rapid PDC activation, whereas MDCs were extremely sensitive to influenza A virus-induced cell death. The most significant differences between DC types were seen in the production of IL-10 and IL-12, which were only produced by S. pyogenes-stimulated MDCs. Although S. pyogenes was able to induce PDC activation, only influenza A virus infection resulted in detectable IFN-{alpha} production. Our results show that depending on the infecting microbe, the functions of PDCs and MDCs may be partially overlapping, suggesting a considerable flexibility of the human DC system.

Key Words: cytokines • bacteria • virus • innate immunity




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