Human neutrophil peptides 1-3 protect the murine urinary tract from uropathogenic challenge.

Antimicrobial peptides (AMPs) are critical to the protection of the urinary tract of humans and other animals from pathogenic microbial invasion. AMPs rapidly destroy pathogens by disrupting microbial membranes and/or augmenting or inhibiting the host immune system through a variety of signaling pathways. We have previously demonstrated that alpha-defensins 1-3 () are AMPs expressed in the epithelial cells of the human kidney collecting duct in response to uropathogens. We also demonstrated that DNA copy number variations in the locus are associated with UTI and pyelonephritis risk. Because is not expressed in mice, we utilized human gene transgenic mice () to further elucidate the biological relevance of this locus in the murine urinary tract. We demonstrate that the kidney transcriptional and translational expression pattern is similar in humans and the human gene transgenic mouse upon uropathogenic (UPEC) stimulus in vitro and in vivo. We also demonstrate transgenic human gene mice are protected from UTI and pyelonephritis under various UPEC challenges. This study serves as the foundation to start the exploration of manipulating the locus and alpha-defensins 1-3 expression as a potential therapeutic target for UTIs and other infectious diseases.