Kidney Week

Abstract: SA-PO604

Ribonuclease 6 Is a Monocyte and Macrophage Derived Antimicrobial Peptide That Limits Urinary Tract Infection Susceptibility In Vivo

Session Information

• Pediatric Nephrology - II
  November 05, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
  Abstract Time: 10:00 AM - 12:00 PM

Category: Pediatric Nephrology

• 1800 Pediatric Nephrology

Authors

• Kercsmar, Macie M., Kidney and Urinary Tract Center, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio, United States

Macie M. Kercsmar,

• Cortado, Hanna H., Kidney and Urinary Tract Center, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio, United States

Hanna H. Cortado,

• Li, Birong, Kidney and Urinary Tract Center, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio, United States

Birong Li,

• Ching, Christina B., Kidney and Urinary Tract Center, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio, United States

Christina B. Ching,

• Jackson, Ashley R., Kidney and Urinary Tract Center, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio, United States

Ashley R. Jackson,

• Spencer, John David, Kidney and Urinary Tract Center, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio, United States

John David Spencer,

• Ruiz-Rosado, Juan de Dios, Kidney and Urinary Tract Center, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio, United States

Juan de Dios Ruiz-Rosado,

• Becknell, Brian, Kidney and Urinary Tract Center, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio, United States

Brian Becknell,

Group or Team Name

• Kidney and Urinary Tract Center

Background

Urinary tract infections (UTI) are common, serious bacterial infections of childhood that originate in the bladder and can ascend to the kidney resulting in acute and chronic injury. Ribonuclease 6 (RNase 6) is an antimicrobial peptide that kills uropathogenic Escherichia coli (UPEC). Here, we studied the impact and cellular sources of RNase6 on UTI susceptibility in vivo.

Methods

To understand the impact of RNase6 on UTI susceptibility, we established humanized RNASE6 transgenic mice and performed transurethral inoculation of UPEC. We utilized a novel Rnase6^EGFP/+ knockin allele and Cx3cr1^GFP/GFP; Ccr2^RFP/RFP mice to definitively establish the cellular sources of RNase6. The role of RNase6 in intracellular UPEC killing was identified in a gentamicin protection assay using bone marrow derived macrophages (BMDM).

Results

RNASE6 transgenic mice were protected from experimental UTI, with reduced bacterial burden throughout the urinary tract, compared to non-transgenic controls. Mouse Rnase6 and human RNase6 are expressed by resident macrophages and circulating monocytes that are recruited to the infected bladder and kidney. At baseline, these RNase6+ cells localize to the submucosa of the bladder and kidney. Following infection, these cells redistribute to the urothelium in close proximity to intracellular UPEC. Compared to non-transgenic controls, RNASE6 transgenic macrophages are more adept at killing phagocytosed UPEC.

Conclusion

RNase6 is a monocyte and macrophage associated antimicrobial peptide that redistributes to the bladder and renal urothelium in the presence of UPEC to effectively limit disseminated infection in vivo.

Funding

• NIDDK Support