Modulation of host innate immune response in the bladder by uropathogenic Escherichia coli
Modulation of host innate immune response in the bladder by uropathogenic Escherichia coli
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DOI：
10.1128/iai.00922-07
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发表时间：
2007-11-01
影响因子：
3.1
通讯作者：
Schaeffer, Anthony J.
中科院分区：
文献类型：
--
作者：
Billips, Benjamin K.;Forrestal, Sarah G.;Schaeffer, Anthony J.
尿路致病性大肠杆菌（UPEC）是尿路感染（UTI）的最常见原因，其与炎症反应相关，所述炎症反应包括诱导尿路上皮细胞分泌细胞因子/趋化因子和向膀胱募集中性粒细胞。然而，最近的研究表明，UPEC可以逃避体外尿路上皮天然免疫反应的早期激活。在这项研究中，我们报告了与1型纤毛大肠杆菌感染相比，感染原型UPEC菌株NU 14抑制了尿路上皮细胞培养物中肿瘤坏死因子α（TNF-α）介导的白细胞介素-8（CXCL-8）和白细胞介素-6（CXCL-6）的分泌。coli K-12菌株。此外，对一组临床E. 17株大肠杆菌中有15株具有抑制细胞因子分泌的能力。在UTI的鼠模型中，相对于用大肠杆菌感染，NU 14感染导致膀胱中编码角化细胞衍生的趋化因子、巨噬细胞炎性肽2和CXCL-6的mRNA水平降低。coli K-12菌株。此外，NU 14感染期间炎性趋化因子产生的刺激减少与膀胱和尿髓过氧化物酶水平降低和细菌定植增加相关。这些数据表明，临床大肠杆菌广泛的系统发育范围。大肠杆菌分离株，包括UPEC，可以逃避激活的先天性免疫反应在泌尿道，从而提供了致病优势。
Uropathogenic Escherichia coli (UPEC), the most frequent cause of urinary tract infection (UTI), is associated with an inflammatory response which includes the induction of cytokine/chemokine secretion by urothelial cells and neutrophil recruitment to the bladder. Recent studies indicate, however, that UPEC can evade the early activation of urothelial innate immune response in vitro. In this study, we report that infection with the prototypic UPEC strain NU14 suppresses tumor necrosis factor alpha (TNF-alpha)-mediated interleukin-8 (CXCL-8) and interieukin-6 (CXCL-6) secretion from urothelial cell cultures compared to infection with a type 1 piliated E. coli K-12 strain. Furthermore, examination of a panel of clinical E. coli isolates revealed that 15 of 17 strains also possessed the ability to suppress cytokine secretion. In a murine model of UTI, NU14 infection resulted in diminished levels of mRNAs encoding keratinocyte-derived chemokine, macrophage inflammatory peptide 2, and CXCL-6 in the bladder relative to infection with an E. coli K-12 strain. Furthermore, reduced stimulation of inflammatory chemokine production during NU14 infection correlated with decreased levels of bladder and urine myeloperoxidase and increased bacterial colonization. These data indicate that a broad phylogenetic range of clinical E. coli isolates, including UPEC, may evade the activation of innate immune response in the urinary tract, thereby providing a pathogenic advantage.