The molecular basis of acute pyelonephritis has been extensively studied in the murine acute pyelonephritis model and in patients with UTI.10,30,31 Uropathogenic E. coli activate a TLR-4-dependent innate immune response and single-gene deletions have identified Tlr4 as an upstream regulator of kidney pathology.32–34 Further studies have shown that transcription factors downstream of Tlr4 regulate disease severity, affecting many of the cytokines identified in this study. The gene discussed is TLR4; the disease is acute pyelonephritis.