Pyelonephritic Escherichia coli expressing P fimbriae decrease immune response of the mouse kidney.
P fimbriae are proteinaceous appendages on the surface of Escherichia coli bacteria that mediate adherence to uroepithelial cells. E. coli that express P fimbriae account for the majority of ascending urinary tract infections in women with normal urinary tracts. The hypothesis that P fimbriae on uropathic E. coli attach to renal epithelia and may regulate the immune response to establish infection was investigated. The polymeric Ig receptor (pIgR), produced by renal epithelia, transports IgA into the urinary space. Kidney pIgR and urine IgA levels were analyzed in a mouse model of ascending pyelonephritis, using E. coli with (P+) and without (P-) P fimbriae, to determine whether P(+) E. coli regulate epithelial pIgR expression and IgA transport into the urine. (P+) E. coli establish infection and persist to a greater amount than P(-) E. coli. P(+)-infected mice downregulate pIgR mRNA and protein levels compared with P(-)-infected or PBS controls at > or =48 h. The decrease in pIgR was associated with decreased urinary IgA levels in the P(+)-infected group at 48 h. pIgR mRNA and protein also decline in P(+) E. coli-infected LPS-hyporesponsive mice. These studies identify a novel virulence mechanism of E. coli that express P fimbriae. It is proposed that P fimbriae decrease pIgR expression in the kidney and consequently decrease IgA transport into the urinary space. This may explain, in part, how E. coli that bear P fimbriae exploit the immune system of human hosts to establish ascending pyelonephritis.
Rice
James C
JC
Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX 77555-0562, USA. jrice@utmb.edu
Peng
Tao
T
Spence
Jeff S
JS
Wang
Hui-Qun
HQ
Goldblum
Randall M
RM
Corthésy
Blaise
B
Nowicki
Bogdan J
BJ
D000818:Animals; D000907:Antibodies, Bacterial / Q000032:analysis; D015152:Blotting, Northern; D004195:Disease Models, Animal; D004926:Escherichia coli / Q000276:immunology / Q000472:pathogenicity*; D005260:Female; D036781:Fimbriae Proteins / Q000276:immunology / Q000378:metabolism*; D010861:Fimbriae, Bacterial / Q000276:immunology / Q000378:metabolism*; D007150:Immunohistochemistry; D051379:Mice; D008809:Mice, Inbred C3H; D011704:Pyelonephritis / Q000382:microbiology* / Q000473:pathology*; D012329:RNA, Bacterial / Q000032:analysis; D012680:Sensitivity and Specificity; D014774:Virulence
D000907:Antibodies, Bacterial; D012329:RNA, Bacterial; D036781:Fimbriae Proteins