Macrophages in the male genital tract.

Abstract

Macrophages play essential roles in maintaining immune defence and tissue homeostasis within the male genital tract, which is essential for reproductive health. Since their initial discovery in the testes, macrophages have been established as highly adaptable immune cells that perform diverse functions ranging from immune surveillance to tissue repair. In the testes, macrophages play a crucial role in maintaining immune privilege and tissue homeostasis by regulating inflammatory responses and supporting steroidogenesis and spermatogenesis via intricate crosstalk with Leydig and Sertoli cells. In the epididymis, macrophages maintain a balance between immune tolerance and pathogen defence, ensuring the integrity of maturing sperm. Moreover, recent evidence has begun to reveal the complex and unique characteristics of prostate tissue-resident macrophages and their roles in homeostasis and disease. Notably, these cells exhibit dual functions in pathological conditions, contributing both to chronic inflammation in prostatitis and to the modulation of tumour dynamics in prostate cancer. Remarkably, dysregulation of macrophage function has been implicated in several prevalent male urological diseases and male infertility. This review integrates historical perspectives with recent advances in the immunobiology of macrophages in the male genital tract, highlighting their role as pivotal regulators of reproductive tract homeostasis.