Cover Image

TIR-domain-containing protein C as modulator of innate immune checkpoints

The TIR-domain-containing protein C (TcpC), a virulence factor of the uropathogenic Escherichia coli strain CFT073, binds to crucial components of the toll-like receptor-signaling cascade and the NLRP3 inflammasome thus manipulating these innate immune checkpoints and their immune responses. Here we...

Full description

Saved in:
Bibliographic Details
Main Authors: Heine, Leon (Author) , Griffiths, Hannah-Miriam (Author) , Hu, Huiyun (Author) , Müller, Isabelle (Author) , Kuhn, Svetlana (Author) , Rudolph, Luca (Author) , Rait, Xaver (Author) , Waldhuber, Anna (Author) , Chen, Ying (Author) , Miethke, Thomas (Author)
Format: Article (Journal)
Language:English
Published: 27 November 2025
In: Scientific reports
Year: 2025, Volume: 15, Issue: 1, Pages: 1-15
ISSN:2045-2322
DOI:10.1038/s41598-025-29677-w
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1038/s41598-025-29677-w
Verlag, kostenfrei, Volltext: https://www.nature.com/articles/s41598-025-29677-w
Get full text
Author Notes:Leon Heine, Hannah Griffiths, Huiyun Hu, Isabelle Müller, Svetlana Kuhn, Luca Rudolph, Xaver Rait, Anna Waldhuber, Ying Chen & Thomas Miethke
Description
Summary:The TIR-domain-containing protein C (TcpC), a virulence factor of the uropathogenic Escherichia coli strain CFT073, binds to crucial components of the toll-like receptor-signaling cascade and the NLRP3 inflammasome thus manipulating these innate immune checkpoints and their immune responses. Here we show that TcpC intensified TLR4-dependent pro-inflammatory cytokine secretion by human epithelial cells upon infection with CFT073. Furthermore, TcpC amplified immune responses of monocytic THP-1 cells and peripheral blood mononuclear cells and monocytes during infection. Interestingly, differentiation of monocytes to M0 macrophages reduced the influence of TcpC on innate immune responses. Similarly, polarization of monocytic THP-1 to M1 macrophages impaired partially the ability of TcpC to modulate cytokine secretion. Induced expression of TcpC revealed that increasing levels of TcpC induction augmented the stimulation of THP-1 cells during infection. In contrast, transfer of TcpC-containing culture supernatants from CFT073 to endotoxin plus ATP-stimulated monocytic THP-1 cells revealed the inhibitory function of TcpC. In summary, we show here that TcpC strengthens cytokine release during infection but dampens it during endotoxin-stimulation.
Item Description:Artikelversion: 28. November 2025
Gesehen am 15.01.2026
Physical Description:Online Resource
ISSN:2045-2322
DOI:10.1038/s41598-025-29677-w

Similar Items