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Human renal fibroblasts are strong immunomobilizers during a urinary tract infection mediated by uropathogenic Escherichia coli
Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Clinical trial unit.ORCID iD: 0000-0003-3869-1903
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Örebro University, School of Medical Sciences. (iRiSC - Inflammatory Response and Infection Susceptibility Centre)
2019 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, no 1, article id 2296Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Nature Publishing Group, 2019. Vol. 9, no 1, article id 2296
National Category
Immunology
Identifiers
URN: urn:nbn:se:oru:diva-72784DOI: 10.1038/s41598-019-38691-8ISI: 000459092800066PubMedID: 30783129Scopus ID: 2-s2.0-85061794911OAI: oai:DiVA.org:oru-72784DiVA, id: diva2:1291843
Note

Funding Agencies:

Research Committee of Örebro County Council  

Faculty of Medicine and Health at Örebro University 

Available from: 2019-02-26 Created: 2019-02-26 Last updated: 2019-06-19Bibliographically approved

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Klarström-Engström, KristinDemirel, Isak

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