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While the early response to UTI is known to be important in combating urinary pathogens, knowledge of host factors that help curb infection is still limited. Here, we use a preclinical model of UTI to study secretory leukocyte protease inhibitor (SLPI), an antimicrobial protein, to determine how it protects the bladder against infection. We find that SLPI is increased during UTI, accelerates the clearance of bacteriuria, and upregulates genes and pathways needed to fight an infection while preventing prolonged bladder inflammation. In a small clinical study, we show SLPI is readily detectable in human urine and is associated with the presence of a uropathogen in patients without a previous history of UTI, suggesting SLPI may play an important role in protecting from bacterial cystitis.<\/jats:p>","DOI":"10.1128\/mbio.02554-23","type":"journal-article","created":{"date-parts":[[2024,1,25]],"date-time":"2024-01-25T09:02:44Z","timestamp":1706173364000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":9,"title":["Secretory leukocyte protease inhibitor protects against severe urinary tract infection in mice"],"prefix":"10.1128","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7656-3382","authenticated-orcid":false,"given":"Anne L.","family":"Rosen","sequence":"first","affiliation":[{"name":"Division of Allergy and Immunology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA"},{"name":"Center 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