Impaired cytokine expression, neutrophil infiltration and bacterial clearance in response to urinary tract infection in diabetic mice
Impaired cytokine expression, neutrophil infiltration and bacterial clearance in response to urinary tract infection in diabetic mice
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DOI：
10.1093/femspd/ftv002
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发表时间：
2015-04-01
影响因子：
3.3
通讯作者：
Daneshgari, Firouz
中科院分区：
文献类型：
--
作者：
Ozer, Ahmet;Altuntas, Cengiz Z.;Daneshgari, Firouz
糖尿病患者对感染的易感性增加，尿路感染（UTI）是女性糖尿病患者最常见的类型。关于糖尿病患者尿路感染后细菌清除效果的了解很少。在这项研究中，在小鼠模型中研究了糖尿病对细菌清除效率和先天免疫系统组成部分对尿路感染的影响。链脲佐菌素诱导的糖尿病小鼠和对照雌性 C57BL/6J 小鼠感染泌尿道致病性大肠杆菌，并研究了膀胱中随时间推移的细菌负荷、趋化因子表达和中性粒细胞浸润。还测量了组蛋白脱乙酰酶的表达水平，以解决表型背后的潜在机制。与对照组相比，糖尿病小鼠尿路感染期间的细菌清除时间显着延长。与对照组相比，糖尿病小鼠在感染后的早期时间点，膀胱组织和尿液中的中性粒细胞浸润以及膀胱组织中趋化因子 MIP-2、KC、MCP-1 和 IL-6 的 mRNA 和蛋白表达均减少。此外，糖尿病小鼠中组蛋白脱乙酰酶 1-5 的 mRNA 水平增加。这是第一项研究表明糖尿病小鼠细菌清除受损与尿路感染诱导的趋化因子表达和膀胱中中性粒细胞浸润的抑制有关。
Diabetic patients have increased susceptibility to infections, and urinary tract infections ( UTI) are the most common type in women with diabetes mellitus. Knowledge of bacterial clearance effectiveness following UTI in diabetics is sparse. In this study, the effects of diabetes on bacterial clearance efficiency and components of the innate immune system in response to UTI in a murine model were investigated. Streptozotocin-induced diabetic and control female C57BL/6J mice were infected with uropathogenic Escherichia coli, and bacterial load, expression of chemokines, and neutrophil infiltration in the bladder over time were investigated. Expression levels of histone deacetylases were also measured to address a potential mechanism underlying the phenotype. Bacterial clearance during UTI was significantly prolonged in diabetic mice relative to controls. Neutrophil infiltration in bladder tissue and urine, and both mRNA and protein expression of chemokines MIP-2, KC, MCP-1 and IL-6 in bladder tissue were diminished at early time points after infection in diabetic mice relative to controls. In addition, mRNA levels of histone deacetylases 1-5 were increased in diabetic mice. This is the first study to show an association of impaired bacterial clearance in diabetic mice with suppression of UTI-induced chemokine expression and neutrophil infiltration in the bladder.