Tamm-Horsfall Protein Protects Against Urinary Tract Infection by Proteus mirabilis

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...