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Published on: June 22, 2016
Human blood mDC subsets exhibit distinct TLR repertoire and responsiveness
Caroline Hémont1, Antoine Neel, Michèle Heslan
1Nantes CHU, Quai Moncousu, Nantes, France. caroline.hemont@chu-nantes.fr
Abstract:
Human blood DCs encompass pDCs and two subsets of mDCs: CD1c(+) mDCs and CD141(+) mDCs. The rare CD141(+) DC population is thought to be the equivalent of mouse CD8α(+) cDCs that play a significant role in antigen cross-presentation. Here, we analyzed by Q-PCR TLR1-10 expression in blood DC subsets. Whereas CD1c(+) DCs express all TLR except TLR9, CD141(+) DCs present a more restricted pattern with high expression of TLR3 and -10, expression of TLR1,-2, -6, and -8, and lack of TLR4, -5, -7, and -9. The in vitro analysis of isolated mDC subset reponsiveness to an extensive panel of TLR ligands confirmed these results, with CD141(+) DCs responding only to TLR1/2, -3, and -7/8. The cytokine/chemokine production profile of isolated CD141(+) DCs was also more restricted, as they produced mainly proinflammatory cytokines but no IL-12 and to a lower level, in comparison with CD1c(+) DCs, except for CXCL10, CCL5, and IFN-β. In contrast, with the use of a whole blood assay, we found that CD141(+) DCs produce IL-12 in response to TLR1/2, -3, and more surprisingly, -9. Finally, both mDC subsets are potent inducers of Th1 response, particularly after TLR3 triggering. Taken together, these data confirmed functional differences between blood mDC subsets. The major response of CD141(+) mDCs to TLR3 ligand and their cytokine production pattern suggest a role for these cells in antiviral immunity.
Insights
Human myeloid dendritic cell (mDC) subsets show distinct Toll-like receptor (TLR) expression and cytokine responses. CD141(+) mDCs, crucial for antiviral immunity, exhibit unique TLR profiles and limited IL-12 production, except when stimulated via TLR9.
Area of Science:
- Immunology
- Cell Biology
- Infectious Disease Research
Background:
- Human blood contains plasmacytoid dendritic cells (pDCs) and two myeloid dendritic cell (mDC) subsets: CD1c(+) mDCs and CD141(+) mDCs.
- The CD141(+) DC subset is considered analogous to mouse CD8α(+) conventional dendritic cells (cDCs), known for their role in antigen cross-presentation.
Purpose of the Study:
- To investigate the Toll-like receptor (TLR) expression profiles of human blood DC subsets.
- To analyze the functional responses and cytokine production of isolated mDC subsets upon TLR stimulation.
- To elucidate the distinct roles of CD1c(+) and CD141(+) mDCs in immune responses, particularly in antiviral immunity.
Main Methods:
- Quantitative PCR (Q-PCR) was used to determine TLR1-10 expression in isolated human blood DC subsets (pDCs, CD1c(+) mDCs, CD141(+) mDCs).
- In vitro stimulation assays with various TLR ligands were performed on isolated mDC subsets to assess their responsiveness.
- Cytokine and chemokine production was analyzed using whole blood assays and from isolated mDC subsets.
- The capacity of mDC subsets to induce T helper 1 (Th1) responses was evaluated, especially after TLR3 triggering.
Main Results:
- CD1c(+) DCs express all TLRs except TLR9, while CD141(+) DCs show a restricted pattern, notably lacking TLR4, -5, -7, and -9, but expressing high levels of TLR3 and -10.
- In vitro, CD141(+) DCs responded only to TLR1/2, -3, and -7/8 ligands, producing mainly pro-inflammatory cytokines but limited IL-12 compared to CD1c(+) DCs.
- Surprisingly, whole blood assays revealed that CD141(+) DCs can produce IL-12 in response to TLR1/2, -3, and TLR9 stimulation.
- Both mDC subsets effectively induce Th1 responses, particularly following TLR3 activation.
Conclusions:
- Significant functional differences exist between human blood CD1c(+) and CD141(+) mDC subsets.
- The strong response of CD141(+) mDCs to TLR3 ligands and their specific cytokine profile suggest a key role in antiviral immunity.
- These findings highlight the specialized functions of distinct DC subsets in orchestrating adaptive immune responses.
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