Kidney Week

Abstract: PO1987

Renal-Derived Alpha-Defensins 1-3 Contribute to Enhanced Urinary Tract Protection in Humanized Mouse Transplant Model Challenged against Uropathogenic Escherichia coli

Session Information

• Pediatric Nephrology: Genetics, Kidney Stones, Quality Improvement, and Case Reports
  November 04, 2021 | Location: On-Demand, Virtual Only
  Abstract Time: 10:00 AM - 12:00 PM

Category: Pediatric Nephrology

• 1700 Pediatric Nephrology

Authors

• Canas, Jorge Jose, Indiana University School of Medicine, Indianapolis, Indiana, United States

Jorge Jose Canas

• Hooks, Jenaya, Indiana University School of Medicine, Indianapolis, Indiana, United States

Jenaya Hooks,

• Arregui, Sam W., Indiana University School of Medicine, Indianapolis, Indiana, United States

Sam W. Arregui,

• Schwaderer, Andrew L., Indiana University School of Medicine, Indianapolis, Indiana, United States

Andrew L. Schwaderer,

• Hains, David S., Indiana University School of Medicine, Indianapolis, Indiana, United States

David S. Hains,

Background

Alpha-defensins 1-3 are potent antimicrobial peptides expressed from DEFA1A3 gene locus by human neutrophils and kidneys. Decreased DNA copy numbers of DEFA1A3 have been associated with UTI susceptibility. Here, we utilize a human DEFA1 knock-in transgenic mouse (Defa⁺) to study the role of DEFA1A3 in UTIs. We hypothesized that DEFA1 protects the murine urinary tract from uropathogenic E. coli (UPEC) challenge and renally derived DEFA1A3 is the protective source.

Methods

Female wild-type (WT) and Defa⁺ mice were infected by transurethral inoculation of UPEC; CFT073, pyelonephritis strain. Bacterial burdens in kidneys and bladders for each group of mice were analyzed at 6 hours post-infection (hpi). We performed transplant isografts of Defa^Kidney → WT^Recipient mice and used WT^Kidney → WT^Recipient as biological controls for UPEC challenges (Figure 1A).

Results

Murine bladder and kidney CFU bacterial burdens results are presented in Figure 1: Comparing the groups at 6 hpi, CFU burden averages were significantly lower in the Defa^Kidney → WT^Recipient infected bladder group, similarly to infected Defa⁺ mice when compared to its WT counterpart (B). Strikingly, kidneys from Defa^Kidney → WT^Recipient were protected against bacterial growth, in contrast to WT^Kidney → WT^Recipient controls, which showed higher titers of CFU burdens per transplanted kidney following pyelonephritis challenge, and recapitulates the protective phenotype observed in the Defa⁺ infected mice when compared to its WT control group (C).

Conclusion

Our findings support the role of renal-derived alpha-defensins 1-3 in not only protecting the transplanted kidney but the entire lower urinary tract from UPEC.

Murine isograft transplant model & CFU bacterial burden results of infected upper and lower urinary tract tissues

Funding

• NIDDK Support