Functionally distinct resident macrophage subsets differentially shape responses to infection in the bladder.

Area of Science:

• Immunology
• Urology
• Cell Biology

Background:

• Resident macrophages are crucial for bladder immunity against uropathogens.
• The heterogeneity, origin, and infection response of bladder macrophages are poorly understood.

Purpose of the Study:

• To investigate the heterogeneity and function of resident bladder macrophages.
• To understand their response to urinary tract infection (UTI) and implications for immunity.

Main Methods:

• Macrophage subset identification using transcriptomics and protein expression in mouse bladders.
• Utilizing a mouse model of urinary tract infection.
• Macrophage depletion experiments to assess immune response and bacterial clearance.

Main Results:

• Two distinct macrophage subsets identified: MacM (muscle) and MacL (lamina propria), with unique transcriptomes.
• MacM macrophages exhibited enhanced bacterial phagocytosis and anti-inflammatory polarization during UTI.
• MacL macrophages showed rapid death during infection; monocyte-derived cells repopulated resident pools.
• Macrophage depletion led to a type 1-biased immune response and improved bacterial clearance upon secondary UTI.

Conclusions:

• Resident bladder macrophages are heterogeneous and exhibit distinct functional roles during infection.
• Understanding these macrophage subsets offers insights into bladder immunity and potential therapeutic strategies for recurrent UTIs.