Department of Clinical trial unit, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Sci Rep. 2019 Feb 19;9(1):2296. 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.
为了预防尿脓毒症的发生并降低死亡率，我们需要更好地了解尿路致病性大肠杆菌（UPEC）如何通过肾脏渗透到血液中。本研究阐明了人类肾间质成纤维细胞是否是限制 UPEC 感染的免疫反应的一部分，或者 UPEC 是否有能力为自身利益调节成纤维细胞。微阵列结果表明，上调的基因与激活的免疫反应有关。我们还发现，UPEC 感染肾成纤维细胞释放的趋化因子可能通过激活 TLR2/1、TLR4、MAPK、NF-κB 和 PKC 信号通路的 LPS 和三酰基脂蛋白介导。此外，研究还表明，UPEC 能够通过 P-菌毛黏附和侵入肾成纤维细胞。此外，研究还发现，与 UPEC 感染后，肾成纤维细胞比肾上皮细胞更具免疫反应性。然而，肾成纤维细胞和上皮细胞在诱导中性粒细胞迁移方面同样有效。总之，我们发现人类肾成纤维细胞可以感知 UPEC 并通过中性粒细胞迁移动员宿主反应。这表明肾成纤维细胞不仅是产生和调节细胞外基质的结构性细胞，而且还是高度免疫反应性的细胞。
