Interleukin-8 receptor knockout mice have subepithelial neutrophil entrapment and renal scarring following acute pyelonephritis

Abstract

Interleukin (IL)-8 receptor knockout (KO) mice were shown to have a dysfunctional neutrophil response to urinary tract infection and to develop renal scarring. Intravesical Escherichia coli infection stimulated epithelial chemokine secretion and IL-8 receptor expression in control mice. Neutrophils migrated through the tissues and crossed the epithelial barrier into the urinary tract lumen. In murine IL-8 receptor homologue (mIL-8Rh) KO mice, infection triggered a chemokine response, and neutrophils were recruited but failed to traverse the mucosal barrier and accumulated under the epithelium. After 7 days, control mice were healthy, and infection was cleared, but mIL-8Rh KO mice had swollen kidneys, with neutrophil abscesses and high numbers of bacteria. After 35 days, they developed kidney pathology and renal scarring. The results demonstrate that chemokine receptors drive transepithelial neutrophil migration. In their absence, the neutrophils are trapped, and the tissues are destroyed. This molecular deficiency may determine the progression from acute pyelonephritis to renal scarring.