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Updated: Oct 18, 2025
Development and Functional Characterization of Murine Tolerogenic Dendritic Cells
Published on: May 18, 2018
Mice Plasmacytoid Dendritic Cells Were Activated by Lipopolysaccharides Through Toll-Like Receptor 4/Myeloid
Wei Zhang1, Eun-Koung An2,3, Juyoung Hwang1,2,3
1Shanghai Public Health Clinical Center, Shanghai Medical College, Fudan University, Shanghai, China.
Abstract:
Plasmacytoid dendritic cells (pDCs) are known to respond to viral infections. However, the activation of pDCs by bacterial components such as lipopolysaccharides (LPS) has not been well studied. Here, we found that pDCs, conventional dendritic cells (cDCs), and B cells express high levels of toll-like receptor 4 (TLR4), a receptor for LPS. Moreover, LPS could effectively bind to not only cDCs but also pDCs and B cells. Intraperitoneal administration of LPS promoted activation of splenic pDCs and cDCs. LPS treatment led to upregulation of interferon regulatory factor 7 (IRF7) and induced production of interferon-alpha (IFN-α) in splenic pDCs. Furthermore, LPS-dependent upregulation of co-stimulatory molecules in pDCs did not require the assistance of other immune cells, such as cDCs. However, the production levels of IFN-α were decreased in cDC-depleted splenocytes, indicating that cDCs may contribute to the enhancement of IFN-α production in pDCs. Finally, we showed that activation of pDCs by LPS requires the TLR4 and myeloid differentiation factor 2 (MD2) signaling pathways. Thus, these results demonstrate that the gram-negative component LPS can directly stimulate pDCs via TLR4/MD2 stimulation in mice.
Insights
Gram-negative bacteria component, lipopolysaccharide (LPS), directly activates plasmacytoid dendritic cells (pDCs) in mice. This activation occurs via Toll-like receptor 4 (TLR4) and myeloid differentiation factor 2 (MD2) signaling pathways, inducing interferon-alpha production.
Area of Science:
- Immunology
- Cell Biology
Background:
- Plasmacytoid dendritic cells (pDCs) are known for their role in antiviral responses.
- The activation of pDCs by bacterial components, like lipopolysaccharides (LPS), is less understood.
Purpose of the Study:
- To investigate the direct activation of pDCs by LPS.
- To elucidate the molecular mechanisms involved in LPS-induced pDC activation.
Main Methods:
- Flow cytometry to assess cell surface marker expression.
- Intraperitoneal LPS administration in mice.
- Analysis of cytokine production (IFN-α) and gene expression (IRF7).
- Depletion of conventional dendritic cells (cDCs) to study their role.
Main Results:
- pDCs, cDCs, and B cells express Toll-like receptor 4 (TLR4), the LPS receptor.
- LPS administration activated splenic pDCs and cDCs, upregulating IRF7 and inducing IFN-α production in pDCs.
- LPS-induced co-stimulatory molecule upregulation on pDCs was independent of cDCs.
- IFN-α production was reduced in cDC-depleted splenocytes, suggesting a supportive role for cDCs.
Conclusions:
- LPS directly stimulates pDCs through the TLR4/MD2 signaling pathway in mice.
- pDCs can be activated by bacterial components, contributing to innate immune responses.
- cDCs may play a role in enhancing LPS-induced IFN-α production by pDCs.
