Immune regulation within the male reproductive tract is necessary for the protection of the spermatogenic cells from a detrimental immune response. This is done by the production of immunomodulatory factors, sequestration of the spermatogenic cells behind the blood-testis barrier (BTB) and blood-epididymal barrier (BEB), and controlled presentation of germ cell antigens. At the same time, bacteria and viruses can take advantage of this unique environment, inducing inflammation and infecting the male reproductive tract, resulting in histological damage, germ cell loss, and potentially leading to infertility. An antimicrobial response is important to counter this affliction that if not properly controlled can lead to germ cell autoimmunity or provide a haven for pathogens. Therefore, the immunomodulatory environment within the testis and epididymis is intrinsically important to maintain this property.