Macrophages and TGFB signaling regulate fibrosis in the Escherichia coli-infected mouse prostate.

Prostate inflammation and fibrosis are linked to lower urinary tract symptoms (LUTS) in men. Uropathogenic Escherichia coli (E. coli) infection of the mouse prostate triggers a cascade of immune responses that drive inflammation and fibrosis. A recent study found that lysosome 2-positive (LYZ2+) myeloid cells (fibrocytes) are recruited in a C-C motif chemokine receptor 2 (Ccr2)-dependent manner to the E. coli-infected prostate, where they produce collagen. This study aims to identify factors that drive collagen synthesis in LYZ2+ myeloid cells during E. coli infection. We show that lymphocyte antigen 6 family member (Ly6C)hi monocytes and their maturation products, Ly6Chi macrophages, infiltrate the E. coli infected prostate in a Ccr2-dependent manner, that monocytes in the infected prostate produce Tgfb1 RNA, and that E. coli infection activates TGFB signaling and collagen synthesis in LYZ2+ cells. Blockade of macrophage colony-stimulating factor (M-CSF), a factor required for monocyte differentiation into macrophages, reduces macrophage density, TGFB signaling in LYZ2+ cells, and collagen density in the E. coli-infected prostate. These findings highlight a critical role of macrophages in activating collagen synthesis in fibrocytes to drive a fibrotic response to E. coli infection in the mouse prostate.NEW & NOTEWORTHY Prostatic/urethral fibrosis is an emerging cause of urinary voiding dysfunction in aging men and has been linked to prostate inflammation, but cellular mediators and mechanisms of this process are incompletely understood. We provide evidence that Ly6Chi monocytes and LYZ2+ myeloid cells are recruited to the E. coli infected mouse prostate. Macrophages in the infected prostate synthesize TGFB1 and stimulate collagen synthesis in LYZ2+ cells.