Work

CARD8 regulates basal inflammatory signaling and UPEC colonization in bladder epithelial cells

Year: 2026

Type: article

Abstract: Background Urinary tract infection (UTI) is commonly caused by uropathogenic Escherichia coli (UPEC), which can modulate epithelial inflammatory responses and invade bladder epithelial cells. Inflammasome-related pathways are important during UPEC infection, but the role of the inflammasome-associated protein CARD8 in bladder epithelial cells remains unknown. The aim of this study was to investigate the role of CARD8 in bladder epithelial cell responses to UPEC infection. Method Human bladder epithelial cells (HBLAK) were transfected with CARD8 siRNA or control siRNA and infected with the UPEC strain CFT073. Inflammatory responses were assessed by RT-qPCR, ELISA, LDH release, caspase-1 activity assay, and western blotting. Bacterial colonization and invasion were analyzed using fluorescence-based and gentamicin protection assays. To evaluate the role of major UPEC virulence factors, cells were infected with CFT073 mutants lacking fimH, pap or hlyA. Results CARD8 knockdown reduced basal IL-1β and NLRP3 mRNA expression, pro-IL-1β and caspase-1 protein levels, and basal IL-1β and IL-8 release. UPEC infection selectively downregulated the 47-kDa CARD8 isoform, and this effect was not dependent on FimH, Pap, TcpC or HlyA. In addition, CARD8 knockdown did not attenuate CFT073-induced IL-1β release, LDH release, or caspase-1 activity. Furthermore, CARD8 knockdown increased CFT073 colonization and invasion and was associated with increased UPK1A mRNA expression. Conclusion This study identifies CARD8 as a novel regulator of bladder epithelial responses to UPEC infection. CARD8 contributes to basal inflammatory signaling and limits bacterial colonization and invasion. This suggests that CARD8 may regulate epithelial immune responses and host-pathogen interactions during UTI.

Source: Molecular Medicine

DOI: 10.1186/s10020-026-01686-z

Authors: Geena V. Paramel, Isak Demirel

Institution: Örebro University

Language: English

Topic: Urinary Tract Infections Management

Subfield: Epidemiology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,190