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

Abstract

Prostate inflammation and fibrosis are linked to lower urinary tract symptoms (LUTS) in men. Uropathogenic() 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 ()-dependent manner to the-infected prostate, where they produce collagen. This study aims to identify factors that drive collagen synthesis in LYZ2+ myeloid cells duringinfection. We show that lymphocyte antigen 6 family member (Ly6C)monocytes and their maturation products, Ly6Cmacrophages, infiltrate theinfected prostate in adependent manner, that monocytes in the infected prostate produceRNA, and thatinfection 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-infected prostate. These findings highlight a critical role of macrophages in activating collagen synthesis in fibrocytes to drive a fibrotic response toinfection in the mouse prostate.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 Ly6Cmonocytes and LYZ2+ myeloid cells are recruited to theinfected mouse prostate. Macrophages in the infected prostate synthesize TGFB1 and stimulate collagen synthesis in LYZ2+ cells.