Prostatic E. coli infection drives CCR2-dependent recruitment of fibrocytes and collagen production.

Prostate fibrosis contributes to lower urinary tract dysfunction (LUTD). To develop targeted treatments for prostate fibrosis, it is necessary to identify cell types and molecular pathways required for collagen production. We used a genetic approach to label and track potential collagen-producing cell lineages in mouse prostate through a round of Escherichia coli (E. coli) UTI89-mediated prostate inflammation. E. coli increases density and collagen production in Gli1+, S100a4+, Lyz2+ and Cd2+ cells, but not Myh11+ or Srd5a2+ cell lineages in the mouse prostate. Molecular phenotyping reveals GLI1+LYZ+S100A4+ cells (fibrocytes) in histologically inflamed human prostate. These fibrocytes co-localize with regions of increased collagen in men with LUTD. Fibrocyte recruitment and collagen synthesis is impaired in Ccr2 null mice but restored by allotransplantation of Rosa-GFP donor bone marrow derived cells. These results reveal that bone marrow derived fibrocytes may be a source of prostatic collagen accumulation.