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Reviews of "Secretory Leukocyte Protease Inhibitor Protects Against Severe Urinary Tract Infection in Mice"

Reviewers: M Hadjifrangiskou & S Reasoner (Vanderbuilt University) | 📗📗📗📗◻️ • N Frimodt-Moller (Copenhagen University Hospitals) | 📘📘📘📘📘

Published onNov 30, 2023
Reviews of "Secretory Leukocyte Protease Inhibitor Protects Against Severe Urinary Tract Infection in Mice"
key-enterThis Pub is a Review of
Secretory Leukocyte Protease Inhibitor Protects Against Severe Urinary Tract Infection in Mice
Secretory Leukocyte Protease Inhibitor Protects Against Severe Urinary Tract Infection in Mice
Description

Abstract 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.

To read the original manuscript, click the link above.

Summary of Reviews: The reviewers found this preprint demonstrating a role for secretory leukocyte protease inhibitor (SLPI) in urinary tract infections to be reliable to strong. While convincingly showing SLPI levels change during infection, inconsistencies between mRNA and protein data raise questions. Reviewers suggested additional experiments in chronic UTI and other urothelial damage conditions to further support the role of SLPI in balancing inflammation.

Reviewer 1 (Maria H… & Seth R…) | 📗📗📗📗◻️

Reviewer 2 (Niels F…) | 📘📘📘📘📘

RR:C19 Strength of Evidence Scale Key

📕 ◻️◻️◻️◻️ = Misleading

📙📙 ◻️◻️◻️ = Not Informative

📒📒📒 ◻️◻️ = Potentially Informative

📗📗📗📗◻️ = Reliable

📘📘📘📘📘 = Strong

To read the reviews, click the links below. 

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