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Abstract: FR-PO1096

The Ribonuclease 6 Antimicrobial Peptide Limits Bacterial Burden During Experimental Pyelonephritis

Session Information

Category: Pediatric Nephrology

  • 1700 Pediatric Nephrology

Authors

  • Cortado, Hanna H., Nationwide Children's Hospital, Columbus, Ohio, United States
  • Jackson, Ashley R., Nationwide Children's Hospital, Columbus, Ohio, United States
  • Li, Birong, Nationwide Children's Hospital, Columbus, Ohio, United States
  • Ching, Christina B., Nationwide Children''s Hospital, Columbus, Ohio, United States
  • Spencer, John David, The Research Institute at Nationwide Children's, Columbus, Ohio, United States
  • Becknell, Brian, Nationwide Children's Hospital, Columbus, Ohio, United States

Group or Team Name

  • Nephrology and Urology Research Affinity Group
Background

Ribonuclease 6 (RNase 6) is an evolutionarily-conserved antimicrobial peptide that kills uropathogenic bacteria at low micromolar concentrations in vitro. Here, we investigated the hypothesis that RNase 6 limits urinary tract colonization by uropathogenic Escherichia coli (UPEC) in vivo.

Methods

We generated mice with a Rnase6EGFP knock-in allele on a C57BL/6J genetic background. We identified cellular sources of RNase6 based on flow cytometry, epifluorescence, and immunofluorescence microscopy. We transurethrally inoculated Rnase6EGFP/EGFP and control female mice with UPEC strain CFT073 and enumerated bacterial burden in urinary tract tissues by homogenization and serial plating.

Results

Flow cytometry in Rnase6EGFP/+ mice identified EGFP expression by circulating Ly6Chi monocytes which were recruited to the infected bladder by 6 hours post inoculation (hpi). In addition, EGFP was expressed by two discrete resident macrophage populations within the kidney. We confirmed Rnase6 deletion in Rnase6EGFP/EGFP mice, which displayed normal urinary tract development, fertility, and hematopoiesis. Rnase6 deficiency led to increased renal and ureteral UPEC burden at 6 and 12 hpi, compared to control mice.

Conclusion

In the infected urinary tract, RNase6 is primarily expressed by resident macrophages and recruited monocytes. We have demonstrated a critical role for RNase 6 in UPEC clearance from the upper urinary tract during ascending UTI in vivo.

Funding

  • Other NIH Support