Role of class II P fimbriae and cytokine response in the pathogenesis of Escherichia coli kidney infection in diabetic mice

Background: The role of class II P fimbriae (P fimbriae II) in diabetic kidney infections is uncertain, although some genetic and epidemiological studies suggest a lower prevalence of P fimbriae II genes in Escherichia coli strains isolated from diabetic patients with complicated kidney infections. Methods: We inoculated a P fimbriae II deficient E. coli (DH5αT) or an isogenic P fimbriae II expressing transformant (DH5αTP) into the bladders of diabetic and non-diabetic BALB/C mice, and sacrificed them after 3 days. The incidence of bladder or kidney infection (≥10³ CFU of E. coli per bladder or kidney), bacteremia (≥10² CFU of E. coli on blood culture plate), kidney pathological score, immunoreactive Histo-score (H-score), and corrected H-score (H-score adjusted for Log₁₀ CFU of bacteria in the kidney) were compared among groups. Results: Diabetic mice were more susceptible to bladder infection than non-diabetic mice with both transformants. The geometric mean of bacteria counts in kidneys was significantly increased only when the diabetic mice were infected with DH5αTP. Among the 4 groups of mice, diabetic mice infected with DH5αTP had the highest incidence of kidney infection and bacteremia, and the highest renal pathology scores. The IL-8 H-score and the corrected IL-6 and IL-8 H-score were significantly lower in diabetic than non-diabetic mice. Conclusion: We concluded that P fimbriae II contribute to the pathogenesis and severity of E. coli kidney infections in diabetic mice. An impaired cytokine response may also contribute to the increased incidence and severity of kidney infections in diabetic hosts.