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 Blood, 30 April 2009, Vol. 113, No. 18, pp. 4232-4239.
Prepublished online as a Blood First Edition Paper on January 27, 2009; DOI 10.1182/blood-2008-10-186890.

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IMMUNOBIOLOGY

Human plasmacytoid dendritic cells are unresponsive to bacterial stimulation and require a novel type of cooperation with myeloid dendritic cells for maturation

Diego Piccioli1, Chiara Sammicheli1, Simona Tavarini1, Sandra Nuti1, Elisabetta Frigimelica1, Andrea G.O. Manetti1, Annalisa Nuccitelli1, Susanna Aprea1, Sara Valentini1, Erica Borgogni1, Andreas Wack1,*, and Nicholas M. Valiante2,*

1 Research Center, Novartis Vaccines and Diagnostics, Siena, Italy; and 2 Research Center, Novartis Vaccines and Diagnostics, Cambridge, MA

Dendritic cell (DC) populations play unique and essential roles in the detection of pathogens, but information on how different DC types work together is limited. In this study, 2 major DC populations of human blood, myeloid (mDCs) and plasmacytoid (pDCs), were cultured alone or together in the presence of pathogens or their products. We show that pDCs do not respond to whole bacteria when cultured alone, but mature in the presence of mDCs. Using purified stimuli, we dissect this cross-talk and demonstrate that mDCs and pDCs activate each other in response to specific induction of only one of the cell types. When stimuli for one or both populations are limited, they synergize to reach optimal activation. The cross-talk is limited to enhanced antigen presentation by the nonresponsive population with no detectable changes in the quantity and range of cytokines produced. We propose that each population can be a follower or leader in immune responses against pathogen infections, depending on their ability to respond to infectious agents. In addition, our results indicate that pDCs play a secondary role to induce immunity against human bacterial infections, which has implications for more efficient targeting of DC populations with improved vaccines and therapeutics.


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