Crosstalk between Toll like receptors and C5a receptor in human monocyte derived DCs suppress inflammatory cytokine production
Abstract
The complement anaphylatoxin, C5a has been implicated in regulation of adaptive immune responses through modulation of APC function as shown mainly in studies in mice. C5a was shown to enhance cytokine production in immature DCs, but the effect of C5a on DC function during DC activation has not been elucidated in human. In this study we investigated the effect of C5a on human monocyte derived DCs when simultaneously stimulated with TLR ligands. While C5a indeed enhanced cytokine production of immature DCs, the addition of C5a inhibited production of IL-12, IL-23 and TNFα induced by various TLR ligands such as LPS, R848 and Pam(3)CSK(4). The inhibitory effect of C5a on LPS induced IL-6 production was less pronounced and LPS induced IL-10 was not affected at all. This indicates that C5aR signaling has a differential effect on human DC differentiation depending on the crosstalk with other receptors. Furthermore we found that C5a affects the LPS induced cytokines in a small time frame, and requires almost concurrent signaling of C5a receptor and TLR4. These data emphasize the complexity of DC regulation by anaphylatoxins. While complement activation may provide proinflammatory signals to immature DCs in the absence of pathogens, the same products may serve to downmodulate or deviate immune responses upon combat against infections. These context depending effects of anaphylatoxins on immune responses may have important implications for the emerging use of complement inhibitors in…
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C5a is essential for the development and regulation of T-cell immunity.
“it is also essential for the development and regulation of T-cell immunity [187,188,189,190,191,192,193].”
From Bruch’s Membrane: A Key Consideration with Complement-Based Therapies for Age-Related Macular Degeneration (2023) · cites this paper as [191]
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- Authors
- Zaal, A., Lissenberg-Thunnissen, S. N., van Schijndel, G., Wouters, D., Ham, S. M. V., & ten Brinke, A.
- Affiliations
- Amsterdam UMC Location University of Amsterdam (NL)
- ORCID
- Ham, S. Marieke van
- Venue
- Immunobiology
- Publisher
- Elsevier BV
- Published
- 2013-02
- Volume
- 218
- Issue
- 2
- Pages
- 175-180
- ISSN
- 0171-2985 (ISSN-L)
- OpenAlex
- W2086302783
- Cited by
- 33
- References
- 27
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 3 · 2023: 1 · 2021: 1 · 2019: 4 · 2018: 3 · 2017: 6 · 2016: 3 · 2015: 3 · 2014: 3 · 2013: 3
- FWCI
- 1.25
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Immunobiology (publishedVersion)
- PubMed (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Pure Amsterdam UMC (submittedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Immunology and Microbiology › Immunology › Complement system in diseases
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- C5a receptor, anaphylatoxins, Toll-like receptors, monocyte-derived dendritic cells, cytokine production, IL-12, IL-23, TNF-α, interleukin-6, IL-10, TLR4, lipopolysaccharide, R848, Pam3CSK4, complement inhibition, immune regulation
- MeSH terms
- Cell Differentiation, Cells, Cultured, Dendritic Cells, Humans, Imidazoles, Immune Tolerance, Lipopolysaccharides, Monocytes, Receptors, Complement, Signal Transduction, Cytokines, Inflammation Mediators, Receptor Cross-Talk, Receptor, Anaphylatoxin C5a, Toll-Like Receptor 4, Lipopeptides
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