Different Roles for Human Lung Dendritic Cell Subsets in Pulmonary Immune Defense Mechanisms
- 1 September 2006
- journal article
- Published by American Thoracic Society in American Journal of Respiratory Cell and Molecular Biology
- Vol. 35 (3), 387-393
- https://doi.org/10.1165/rcmb.2005-0382oc
Abstract
Dendritic cells (DC) have a central role in the initiation of adequate immune responses. They recognize pathogens by means of Toll- like receptors (TLR) and link innate to adaptive immune responses by releasing proinflammatory cytokines and inducing T cell prolifer- ation. We conducted this study to evaluate the expression and function of TLR on human lung DC subsets and to study their T cell stimulatory capacity. TLR gene expression by human pulmonary DCwas evaluatedbyRT-PCR, whileproteinexpression wasanalyzed by flow cytometry. We investigated cytokine release by DC in re- sponse to different TLR ligands. T cell stimulatory capacity was evaluated by mixed leukocyte reactions of purified lung DC with allogeneic T cells. Myeloid dendritic cells type 1 (mDC1) and my- eloid dendritic cells type 2 (mDC2) express mRNA transcripts for TLR1, TLR2, TLR3, TLR4, TLR6, and TLR8. Flow cytometric analysis demonstrated high TLR2 protein expression for mDC1 and moder- ate TLR4 expression for mDC2. mDC1 and mDC2 release proinflam- matory cytokines (TNF-, IL-1, IL-6, and IL-8) in response to TLR2 and TLR4 ligands. TLR3 ligands induce cytokine release in mDC1, but not in mDC2. Plasmacytoid DC (pDC) express TLR7 and TLR9 and release proinflammatory cytokines in response to imiquimod and IFN- in response to CpG oligonucleotides. mDC1 are strong inducers of T cell proliferation, while pDC hardly induce any T cell proliferation. mDC2 have an intermediate T cell-stimulatory capacity. Our results show divergent roles for the different humanKeywords
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