Abstract
Understanding how uropathogenic Escherichia coli (UPEC) modulates the immune response in the kidney is essential to prevent UPEC from reaching the bloodstream and causing urosepsis. The purpose of this study was to elucidate if renal fibroblasts can release IL-1β during a UPEC infection and to investigate the mechanism behind the IL-1β release. We found that the UPEC strain CFT073 induced an increased IL-1β and LDH release from renal fibroblasts, but not from renal epithelial cells. The UPEC-induced IL-1β release was found to be NLRP3, caspase-1, caspase-4, ERK 1/2, cathepsin B and serine protease dependent in renal fibroblasts. We also found that the UPEC virulence factor α-hemolysin was necessary for IL-1β release. Conditioned medium from caspase-1, caspase-4 and NLRP3-deficient renal fibroblasts mediated an increased reactive oxygen species production from neutrophils, but reduced UPEC phagocytosis. Taken together, our study demonstrates that renal fibroblasts, but not renal epithelial cells, release IL-1β during a UPEC infection. This suggest that renal fibroblasts are vital immunoreactive cells and not only structural cells that produce and regulate the extracellular matrix.
Highlights
Urinary tract infection (UTI) is one of the most common infections in humans and it is primarily caused by uropathogenic Escherichia coli (UPEC) [1,2]
The human renal fibroblast cell line TK173, the human renal epithelial cell line A498 and the human immortalized proximal tubule epithelial cell line HK-2 were infected with CFT073 and the release of IL-1β and Lactate dehydrogenase (LDH) was assessed
We found that CFT073 significantly increased the release of IL-1β from renal fibroblasts at multiplicity of infection (MOI) 1 and 10 after 6 h of infection compared to unstimulated cells (Figure 1A)
Summary
Urinary tract infection (UTI) is one of the most common infections in humans and it is primarily caused by uropathogenic Escherichia coli (UPEC) [1,2]. The infection can develop into a complicated UTI that can lead to pyelonephritis, bacteremia and urosepsis. Acute pyelonephritis often requires hospitalization and when accompanied by bacteremia, acute pyelonephritis has a mortality rate of 10% to 20% [3]. Every year approximately 30 million people are afflicted by sepsis, which has a mortality rate of 30–40% [6,7]. We need a better understanding of how UPEC bacteria modulate the immune responses in the kidney and bloodstream, in order to prevent bacterial infiltration into the bloodstream from the kidneys. This knowledge could help us prevent the onset of urosepsis and reduce mortality
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