Innate immunity of surfactant proteins A and D in urinary tract infection with uropathogenic Escherichia coli.
Innate immunity of surfactant proteins A and D in urinary tract infection with uropathogenic Escherichia coli.
复制标题
尿路致病性大肠杆菌尿路感染中表面活性蛋白 A 和 D 的先天免疫。
DOI：
10.1177/1753425915609973
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发表时间：
2016-01
期刊：
影响因子：
3.2
通讯作者：
Wang G
中科院分区：
文献类型：
--
作者：
Hu F;Ding G;Zhang Z;Gatto LA;Hawgood S;Poulain FR;Cooney RN;Wang G
为了研究表面活性剂蛋白A和D （SP-A, SP-D）在尿路感染（UTI）中的作用，采用膀胱内接种SP-A和SP-D双敲除（SP-A/D KO）和野生型（WT） C57BL/6雌性小鼠感染尿路致病性大肠杆菌。与WT小鼠相比，SP-A/D KO小鼠对UTI的易感性增加，表现为更高的细菌CFU，更多的浸润性中性粒细胞和严重的病理改变。感染24小时后，角质细胞来源的趋化因子在WT小鼠肾脏中升高，而在SP-A/D KO小鼠肾脏中没有升高。与对照组相比，感染WT和SP-A/D KO小鼠肾脏中IL-17水平升高，且感染24和48 h后SP-A/D KO小鼠的IL-17水平高于感染WT小鼠。SP-A/D KO小鼠p38 MAPK磷酸化的基础水平高于WT小鼠。感染后WT小鼠肾脏中磷酸化p38水平升高，而SP-A/D KO小鼠肾脏中磷酸化p38水平未升高。此外，SP-A和SP-D还能抑制尿路致病性大肠杆菌的体外生长。我们得出结论，SP-A和SP-D作为先天免疫的介质，通过抑制细菌生长和部分通过调节小鼠UTI中的p38 mapk相关途径调节肾脏炎症。
To investigate the effects of surfactant proteins A and D (SP-A, SP-D) in urinary tract infection (UTI), SP-A and SP-D double knockout (SP-A/D KO) and wild type (WT) C57BL/6 female mice were infected with uropathogenic Escherichia coli by intravesical inoculation. Compared with WT mice SP-A/D KO mice showed increased susceptibility to UTI as evidenced by higher bacterial CFU, more infiltrating neutrophils and severe pathological changes. Keratinocyte-derived chemokine increased in the kidney of WT mice but not in SP-A/D KO mice 24 h post-infection. Compared to control, level of IL-17 was elevated in the kidney of infected WT and SP-A/D KO mice and the level of IL-17 was higher in the infected SP-A/D KO mice than infected WT mice 24 and 48 h post-infection. Basal level of p38 MAPK phosphorylation in SP-A/D KO mice was higher compared to WT mice. Phosphorylated-p38 level was elevated in the kidney of WT mice post-infection but not in SP-A/D KO mice. Furthermore, in vitro growth of uropathogenic E. coli was inhibited by SP-A and SP-D. We conclude that SP-A and SP-D function as mediators of innate immunity by inhibiting bacterial growth and modulating renal inflammation in part by regulating p38 MAPK-related pathway in murine UTI.