Deficiency of DNASE1 and DNASE1L3 promotes DNA-containing bacterial lesions in the kidney. WT or D1−/−D1L3−/− double-knockout (DKO) mice were infected i.v. with 1 × 107 CFU of S. aureus, and their kidneys were examined 72 h later. (A–C) Scanning EM of kidney tissue from uninfected (UI) WT mice (A), infected WT mice (B), and infected DKO mice (C). Shown are low-magnification images of the kidney and magnified images of areas in white boxes (scale bars, 10 μm). An additional magnified image of the bacterial lesion in DKO mice (yellow box) is shown with pseudocolored clusters of planctonic S. aureus (purple) and biofilm-like structures comprised of bacteria and extracellular matrix (yellow). Representative of 10–12 magnified areas per kidney from two mice per condition/genotype. (D and E) Immunohistochemistry of kidney sections from infected WT (D) and DKO (E) mice stained with anti–S. aureus antibody and DAPI. Shown are low magnification (4×) images of the entire kidney (scale bar, 1 mm) and magnified images of areas in white boxes (scale bars, 50 μm). The images are representative of eight mice per genotype analyzed in two independent experiments. (F) Quantification of S. aureus–positive area in kidney sections. Symbols represent individual mice; bars represent median. Dotted line represents the mean value of uninfected WT mice. Statistical significance was determined by Mann–Whitney test; two-tailed P value < 0.001 (***).
