Secretory Leukocyte Protease Inhibitor Protects Against Severe Urinary Tract Infection in Mice.

Autor:	Rosen AL; Division of Allergy and Immunology, Department of Medicine, Washington University School of Medicine, St. Louis, MO.; Center for Women's Infectious Disease Research, Washington University School of Medicine, St. Louis, MO., Lint MA; Division of Allergy and Immunology, Department of Medicine, Washington University School of Medicine, St. Louis, MO.; Center for Women's Infectious Disease Research, Washington University School of Medicine, St. Louis, MO., Voelker DH; Division of Allergy and Immunology, Department of Medicine, Washington University School of Medicine, St. Louis, MO.; Center for Women's Infectious Disease Research, Washington University School of Medicine, St. Louis, MO., Gilbert NM; Division of Infectious Diseases, Department of Pediatrics, Washington University School of Medicine, St. Louis, MO., Tomera CP; Division of Allergy and Immunology, Department of Medicine, Washington University School of Medicine, St. Louis, MO.; Center for Women's Infectious Disease Research, Washington University School of Medicine, St. Louis, MO., Santiago-Borges J; Division of Allergy and Immunology, Department of Medicine, Washington University School of Medicine, St. Louis, MO.; Center for Women's Infectious Disease Research, Washington University School of Medicine, St. Louis, MO., Wallace MA; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO., Hannan TJ; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO., Burnham CD; Division of Infectious Diseases, Department of Pediatrics, Washington University School of Medicine, St. Louis, MO.; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO.; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO.; Department of Medicine, Washington University School of Medicine, St. Louis, MO., Hultgren SJ; Center for Women's Infectious Disease Research, Washington University School of Medicine, St. Louis, MO.; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO., Kau AL; Division of Allergy and Immunology, Department of Medicine, Washington University School of Medicine, St. Louis, MO.; Center for Women's Infectious Disease Research, Washington University School of Medicine, St. Louis, MO.; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2023 Oct 13. Date of Electronic Publication: 2023 Oct 13.
DOI:	10.1101/2023.10.10.561753
Abstrakt:	Millions suffer from urinary tract infections (UTIs) worldwide every year with women accounting for the majority of cases. Uropathogenic Escherichia coli (UPEC) causes most of these primary infections and leads to 25% becoming recurrent or chronic. To repel invading pathogens, the urinary tract mounts a vigorous innate immune response that includes the secretion of antimicrobial peptides (AMPs), rapid recruitment of phagocytes and exfoliation of superficial umbrella cells. Here, we investigate secretory leukocyte protease inhibitor (SLPI), an AMP with antiprotease, antimicrobial and immunomodulatory functions, known to play protective roles at other mucosal sites, but not well characterized in UTIs. Using a mouse model of UPEC-caused UTI, we show that urine SLPI increases in infected mice and that SLPI is localized to bladder epithelial cells. UPEC infected SLPI-deficient ( Slpi -/- ) mice suffer from higher urine bacterial burdens, prolonged bladder inflammation, and elevated urine neutrophil elastase (NE) levels compared to wild-type ( Slpi +/+ ) controls. Combined with bulk bladder RNA sequencing, our data indicate that Slpi -/- mice have a dysregulated immune and tissue repair response following UTI. We also measure SLPI in urine samples from a small group of female subjects 18-49 years old and find that SLPI tends to be higher in the presence of a uropathogen, except in patients with history of recent or recurrent UTI (rUTI), suggesting a dysregulation of SLPI expression in these women. Taken together, our findings show SLPI protects against acute UTI in mice and provides preliminary evidence that SLPI is likewise regulated in response to uropathogen exposure in women. Competing Interests: Competing Interests The authors do not have any competing interests to report.
Databáze:	MEDLINE
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