A dense and heterogeneous network of mononuclear phagocytes populates the mouse epididymis. Epididymal mononuclear phagocytes (eMPs) expressing macrophage and dendritic cell markers such as CD11c, F4/80, and CX3CR1, line the base of the epididymal tubule and are also present in the interstitium. In the most proximal region of the duct named initial segment (IS), epididymal MPs establish extremely close interactions with the epithelium by projecting slender dendrites between neighboring cells. The overall goal of our project is to elucidate the functions of eMPs in this poorly studied mucosal system.

When we challenged the epididymis by performing efferent duct ligation (EDL), apoptotic epithelial cells were rapidly engulfed and cleared by eMPs. Although apoptotic cell clearance is essential for the maintenance of all epithelia, it is also involved in the maintenance of self-tolerance under physiological conditions. A putative "quality control" of spermatozoa in the epididymis is controversial, however we have clearly demonstrated that the most proximal segment of the mouse epididymis is populated by MPs that project dendrites toward the lumen (and, therefore, toward sperm) and exhibit both phagocytic and antigen-presenting capabilities. We demonstrated, using microscopy and imaging flow cytometry, that isolated eMPs rapidly engulf mouse spermatozoa in vitro. We have also developed a micro-inoculation technique that allows injecting labeled particles and soluble antigens into the lumen of the IS to study antigen uptake and processing in vivo. Our results show that eMPs take up luminal antigens and, possibly, spermatozoa.

We will discuss our most recent results about antigen uptake by eMPs, as well as eMPs interactions with blood and lymphatic vessels. By contributing to the homeostasis of the blood epididymis barrier, the maintenance of a pathogen-free environment and possibly establishing immunological tolerance to sperm antigens, eMPs are likely to be key regulators of the male reproductive function.

This work is supported by the National Institutes of Health grant R01HD069623.

https://csb.mgh.harvard.edu/da_silva