Do type 1 fimbriae promote inflammation in the human urinary tract?
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.
Bergsten
Göran
G
Department of Microbiology, Immunology, and Glycobiology, Lund University, Lund, Sweden.
Wullt
Björn
B
Schembri
Mark A
MA
Leijonhufvud
Irene
I
Svanborg
Catharina
C
D000818:Animals; D001422:Bacterial Adhesion; D002460:Cell Line; D004926:Escherichia coli / Q000378:metabolism / Q000472:pathogenicity*; D004927:Escherichia coli Infections / Q000382:microbiology / Q000503:physiopathology; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D036781:Fimbriae Proteins / Q000235:genetics / Q000378:metabolism; D010861:Fimbriae, Bacterial / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000382:microbiology / Q000503:physiopathology*; D051379:Mice; D008809:Mice, Inbred C3H; D014551:Urinary Tract / Q000276:immunology / Q000382:microbiology* / Q000503:physiopathology*; D014552:Urinary Tract Infections / Q000382:microbiology / Q000503:physiopathology*
D029968:Escherichia coli Proteins; D049452:Green Fluorescent Proteins; D036781:Fimbriae Proteins