Human renal fibroblasts are strong immunomobilizers during a urinary tract infection mediated by uropathogenic Escherichia coli

• Published in: Scientific reports 2019-02, Vol.9 (1), p.2296-2296, Article 2296
• Main Authors: Klarström Engström, Kristin, Zhang, Boxi, Demirel, Isak
• Format: Article
• Language: English
• Subjects: 13/1; 13/21; 14/63; 38/39; 38/77; 631/250/254; 631/326/88; Chemokines; E coli; Epithelial cells; Escherichia coli; Extracellular matrix; Fibroblasts; Humanities and Social Sciences; Immune response; Infections; Kidneys; Leukocyte migration; Lipopolysaccharides; Lipoproteins; MAP kinase; Medicin och hälsovetenskap; multidisciplinary; Neutrophils; NF-κB protein; Pili; Protein kinase C; Science; Science (multidisciplinary); TLR2 protein; TLR4 protein; Toll-like receptors; Urinary tract
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-38691-8

To prevent the onset of urosepsis and reduce mortality, a better understanding of how uropathogenic Escherichia coli (UPEC) manages to infiltrate the bloodstream through the kidneys is needed. The present study elucidates if human renal interstitial fibroblasts are part of the immune response limiting a UPEC infection, or if UPEC has the ability to modulate the fibroblasts for their own gain. Microarray results showed that upregulated genes were associated with an activated immune response. We also found that chemokines released from renal fibroblasts upon a UPEC infection could be mediated by LPS and triacylated lipoproteins activating the TLR2/1, TLR4, MAPK, NF-κB and PKC signaling pathways. Furthermore, UPEC was also shown to be able to adhere and invade renal fibroblasts, mediated by the P-fimbriae. Furthermore, it was found that renal fibroblasts were more immunoreactive than renal epithelial cells upon a UPEC infection. However, both renal fibroblasts and epithelial cells were equally efficient at inducing neutrophil migration. In conclusion, we have found that human renal fibroblasts can sense UPEC and mobilize a host response with neutrophil migration. This suggests that renal fibroblasts are not only structural cells that produce and regulate the extracellular matrix, but also highly immunoreactive cells.