Tamm-horsfall protein protects against urinary tract infection by proteus mirabilis

J Urol. 2009 May;181(5):2332-8. doi: 10.1016/j.juro.2009.01.014. Epub 2009 Mar 19.

Abstract

Purpose: Proteus mirabilis is a common cause of urinary tract infection. We determined the role of Tamm-Horsfall protein as a host defense factor against the cystitis and pyelonephritis caused by P. mirabilis.

Materials and methods: We generated Tamm-Horsfall protein gene knockout mice using homologous recombination. We introduced P. mirabilis transurethrally into the bladder of Tamm-Horsfall protein deficient (THP(-/-)) and genetically similar WT (THP(+/+)) mice. We cultured urine to quantitate the degree of bacteriuria. We examined bladders and kidneys grossly and histomorphometrically to determine the intensity of inflammation.

Results: THP(-/-) mice had more severe bacteriuria and cystitis than THP(+/+) mice. THP(-/-) mice had more pyelonephritic abscesses than THP(+/+) mice. The severity of histological pyelonephritis on semiquantitative histomorphometric analysis appeared to be greater in THP(-/-) mice. The difference between the 2 groups approached but did not attain statistical significance (p = 0.053).

Conclusion: Tamm-Horsfall protein acts as a host defense factor against P. mirabilis induced urinary tract infection.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Bacteriuria / genetics
  • Bacteriuria / physiopathology
  • Biopsy, Needle
  • Cystitis / genetics
  • Cystitis / pathology*
  • Cystitis / prevention & control*
  • Disease Models, Animal
  • Genetic Markers
  • Genetic Predisposition to Disease
  • Immunohistochemistry
  • Mice
  • Mice, Knockout
  • Mucoproteins / genetics*
  • Mucoproteins / metabolism
  • Probability
  • Proteus Infections / genetics
  • Proteus Infections / physiopathology
  • Proteus Infections / prevention & control*
  • Proteus mirabilis / pathogenicity
  • Random Allocation
  • Sensitivity and Specificity
  • Statistics, Nonparametric
  • Urinary Tract Infections / genetics
  • Urinary Tract Infections / pathology
  • Urinary Tract Infections / prevention & control
  • Uromodulin

Substances

  • Genetic Markers
  • Mucoproteins
  • Umod protein, mouse
  • Uromodulin