Two populations of self-maintaining monocyte-independent macrophages exist in adult epididymis and testis

Macrophages are the principal immune cells of the epididymis and testis, but their origins, heterogeneity, development, and maintenance are not well understood. Here, we describe distinct populations of epididymal and testicular macrophages that display an organ-specific cellular identity. Combining in vivo fate-mapping, chimeric and parabiotic mouse models with in-depth cellular analyses, we found that CD64(hi)MHCII(lo )nd CD64(lo)MHCII(hi) macrophage populations of epididymis and testis arise sequentially from yolk sac erythro-myeloid progenitors, embryonic hematopoiesis, and nascent neonatal monocytes. While monocytes were the major developmental source of both epididymal and testicular macrophages, both populations self-maintain in the steady-state independent of bone marrow hematopoietic precursors. However, after radiation-induced macrophage ablation or during infection, bone marrow-derived circulating monocytes are recruited to the epididymis and testis, giving rise to inflammatory macrophages that promote tissue damage. These results define the layered ontogeny, maintenance and inflammatory response of macrophage populations in the male reproductive organs.

Automated summary

Macrophages in the testis and epididymis originate from different stages of cell development and can self-maintain independently of bone marrow hematopoietic cells in a steady state. However, during radiation-induced macrophage ablation or infection, bone marrow-derived cells are recruited to the testis and epididymis, leading to an inflammatory response.