Do type 1 fimbriae promote inflammation in the human urinary tract?

Do type 1 fimbriae promote inflammation in the human urinary tract?
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DOI:
10.1111/j.1462-5822.2007.00912.x
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发表时间:
2007-07-01
影响因子:
3.4
通讯作者:
Svanborg, Catharina
Svanborg, Catharina
中科院分区:
生物学2区
文献类型:
--
作者:
Bergsten, Goran;Wullt, Bjorn;Svanborg, Catharina

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1型菌毛在尿路感染(UTI)的动物模型中被认为是毒力因子,但在人类疾病中的功能仍不清楚。这项研究使用了一个人类激发模型来检查1型菌毛是否会引发尿路炎症。无症状菌尿症菌株大肠杆菌83972,它不能表达1型菌毛,由于一个4.25 kb的fimB-fimD缺失,重建与功能fim基因簇和菌毛表达通过gfp报告监测。每例患者在不同的情况下接种fim+或fim-变体,并通过个体内比较对fim+或fim-同功因子的反应,以细胞因子和中性粒细胞为终点,定量宿主对1型菌毛的反应。1型菌毛不促进炎症和粘附性差,检查尿脱落细胞。这是出乎意料的,因为1型菌毛增强了小鼠泌尿道中对相同菌株的炎症反应,并且E. coli 83972增强了感染患者的粘附和炎症。我们的结论是,1型菌毛不有助于在人类泌尿道粘膜炎症反应。
Type 1 fimbriae have been implicated as virulence factors in animal models of urinary tract infection (UTI), but the function in human disease remains unclear. This study used a human challenge model to examine if type 1 fimbriae trigger inflammation in the urinary tract. The asymptomatic bacteriuria strain Escherichia coli 83972, which fails to express type 1 fimbriae, due to a 4.25 kb fimB-fimD deletion, was reconstituted with a functional fim gene cluster and fimbrial expression was monitored through a gfp reporter. Each patient was inoculated with the fim+ or fim- variants on separate occasions, and the host response to type 1 fimbriae was quantified by intraindividual comparisons of the responses to the fim+ or fim- isogens, using cytokines and neutrophils as end-points. Type 1 fimbriae did not promote inflammation and adherence was poor, as examined on exfoliated cells in urine. This was unexpected, as type 1 fimbriae enhanced the inflammatory response to the same strain in the murine urinary tract and as P fimbrial expression by E. coli 83972 enhances adherence and inflammation in challenged patients. We conclude that type 1 fimbriae do not contribute to the mucosal inflammatory response in the human urinary tract.