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Published ahead of print on October 19, 2005
J Am Soc Nephrol 16: 3583-3591, 2005
© 2005 American Society of Nephrology
doi: 10.1681/ASN.2005030243

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Basic Immunology and Pathology

Pyelonephritic Escherichia coli Expressing P Fimbriae Decrease Immune Response of the Mouse Kidney

James C. Rice*, Tao Peng*, Jeff S. Spence*, Hui-Qun Wang{dagger}, Randall M. Goldblum{ddagger}, Blaise Corthésy§ and Bogdan J. Nowicki||

Departments of * Internal Medicine, {dagger} Research Histopathology, {ddagger} Pediatrics, || Obstetrics and Gynecology and Microbiology and Immunology, The University of Texas Medical Branch at Galveston, Texas; and § Division of Immunology and Allergy, Centre Hospitalier Universitaire Vaudois at Lausanne, Lausanne, Switzerland

Address correspondence to: Dr. James C. Rice, JSA 4.200, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555-0562. Phone: 409-772-1811; Fax: 409-772-5451; E-mail: jrice{at}utmb.edu

Received for publication March 3, 2005. Accepted for publication August 26, 2005.

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 ≥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.




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A. Stapleton
Novel Mechanism of P-Fimbriated Escherichia coli Virulence in Pyelonephritis
J. Am. Soc. Nephrol., December 1, 2005; 16(12): 3458 - 3460.
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