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Updated: May 25, 2025
Quantitative Assessment of Human Neutrophil Migration Across a Cultured Bladder Epithelium
Published on: November 7, 2013
A bladder-blood immune barrier constituted by suburothelial perivascular macrophages restrains uropathogen
Lu Li1, Qiancheng Jiao2, Qianqian Yang3
1National Key Laboratory of Immune responses and Immunotherapy, Department of Oncology, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei 230001, China.
Abstract:
Urinary tract infections (UTIs) predominantly occur in the bladder and can potentially progress into life-threatening sepsis if uropathogens spread unconstrainedly into the bloodstream. Here, we identified a subset of suburothelial perivascular macrophages (suPVMs) in the bladder that exerted a pivotal barrier function to prevent systemic bacterial dissemination during acute cystitis. During the initial phase of uropathogenic Escherichia coli (UPEC) infection, suPVMs actively captured UPEC invading the laminal propria and maintained the integrity of inflamed vessels. They subsequently underwent METosis to expel macrophage extracellular DNA traps (METs) into the urothelium to sequester bacteria within this avascular compartment. Matrix metallopeptidase-13 was released along with METs to promote neutrophil transuroepithelial migration. Replenished suPVMs from monocytes following a prior infection were functionally competent to confer protection against recurrent UTIs. Our study thus uncovers a bladder-blood immune barrier in restraining uropathogen dissemination, which could have implications for the prevention and treatment of urosepsis.
Insights
Suburothelial perivascular macrophages (suPVMs) in the bladder form a critical immune barrier, preventing bacteria from entering the bloodstream during urinary tract infections (UTIs). These cells trap pathogens and release DNA traps to halt infection spread, offering protection against recurrent UTIs.
Area of Science:
- Immunology
- Microbiology
- Urology
Background:
- Urinary tract infections (UTIs) are common and can lead to sepsis.
- Uropathogens can spread from the bladder to the bloodstream, causing severe illness.
- The bladder's defense mechanisms against systemic bacterial spread are not fully understood.
Purpose of the Study:
- To identify immune cells in the bladder that prevent bacterial dissemination.
- To elucidate the mechanisms by which the bladder restricts uropathogen spread.
- To explore the role of these cells in protection against recurrent UTIs.
Main Methods:
- Investigated bladder immune cells during acute cystitis caused by uropathogenic Escherichia coli (UPEC).
- Utilized microscopy and cellular assays to observe macrophage behavior and extracellular DNA trap formation.
- Assessed the role of matrix metallopeptidase-13 in neutrophil migration.
- Evaluated the protective capacity of replenished macrophages against recurrent UTIs.
Main Results:
- Identified suburothelial perivascular macrophages (suPVMs) as key players in preventing bacterial spread.
- suPVMs captured invading UPEC and maintained vascular integrity.
- suPVMs underwent METosis, expelling macrophage extracellular DNA traps (METs) to sequester bacteria.
- Matrix metallopeptidase-13 facilitated neutrophil migration into the urothelium.
- Monocyte-derived suPVMs provided protection against recurrent UTIs.
Conclusions:
- Discovered a bladder-blood immune barrier mediated by suPVMs.
- suPVMs are crucial in preventing uropathogen dissemination and sepsis.
- This barrier mechanism has implications for preventing and treating urosepsis.
- Understanding this barrier may lead to new therapeutic strategies for UTIs.
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