Study on local immune response in diabetic mice, in which bactericidal capacity of the neutrophils had been damaged--Escherichia coli induced experimental urinary tract infection

Abstract

An experimental ascending urinary tract infection was induced by transurethral instillation of Escherichia coli in streptozotocin (STZ)-induced diabetic mice, in which bactericidal capacity of the perineal exudating neutrophils had been damaged. The local immune response in uninfected diabetic mice and the response time fluctuation of local immune responses in diabetic mice following infection were compared with those in normal mice, and the nature of induced changes in the local immune response was determined. The diabetic model was prepared by a single administration of 280 mg/kg of STZ after it had been fasted for 15 hours. The mouse was then fasted an additional 2 hours to induce the diabetic state. Compared with the normal mice, the diabetic mice prepared using this method were found to have a significant suppression of the bactericidal capacity of the perineal exudating neutrophils, 3 weeks after induction of diabetes. The study of the cellular distribution in uninfected urinary tract tissue demonstrated a reduction in CD4-positive T cell distribution in bladder submucosa of diabetic mice at 3 weeks after induction of diabetes (diabetic group), compared with that in the normal mice (control group). In the diabetic group, probably in order to compensate for the reduction in CD4-positive T cell distribution in the bladder submucosa, the distribution of macrophages was increased in the bladder epithelium, compared with the control group. This finding suggested that diabetic mice are thought to have protective mechanisms against infection different from those of normal mice in the uninfected state. The study of the response time fluctuation of local immune response at the infected sites demonstrated infiltration of macrophages was the same grade as that of neutrophils in the control and the diabetic group. However, in the diabetic group, a marked infiltration of macrophages was recognized when compared with the control group in the early phase of infection. These findings suggested that macrophages aid in protection against infection when damage to the bactericidal capacity of neutrophils results in insufficient elimination of microorganisms. On the other hand, infiltration of T and B cells was weaker in the diabetic group, than in the control group.