Bergsten Göran, Wullt Björn, Schembri Mark A, Leijonhufvud Irene, Svanborg Catharina
Department of Microbiology, Immunology, and Glycobiology, Lund University, Lund, Sweden.
Cell Microbiol. 2007 Jul;9(7):1766-81. doi: 10.1111/j.1462-5822.2007.00912.x. Epub 2007 Mar 13.
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.
1型菌毛已被认为是尿路感染（UTI）动物模型中的毒力因子，但在人类疾病中的作用仍不清楚。本研究使用人类激发模型来检测1型菌毛是否会引发尿路炎症。无症状菌尿菌株大肠杆菌83972因4.25 kb的fimB - fimD缺失而无法表达1型菌毛，用功能性fim基因簇进行重建，并通过绿色荧光蛋白（gfp）报告基因监测菌毛表达。每位患者在不同时间分别接种fim +或fim -变体，并以细胞因子和中性粒细胞为终点，通过对fim +或fim -同基因菌应答的个体内比较来量化宿主对1型菌毛的反应。如对尿中脱落细胞检测所示，1型菌毛并未促进炎症，且黏附性较差。这出乎意料，因为1型菌毛可增强同一菌株在小鼠尿路中的炎症反应，而且大肠杆菌83972表达P菌毛可增强激发患者中的黏附性和炎症。我们得出结论，1型菌毛对人类尿路黏膜炎症反应没有作用。
