The Good, the Bad and the Ugly of Testicular Immune Regulation: A Delicate Balance Between Immune Function and Immune Privilege.

The testis is one of several immune privilege sites. These sites are necessary to decrease inflammation and immune responses that could be damaging to the host. For example, inflammation in the brain, eye or placenta could result in loss of cognitive function, vision or rejection of the semi-allogeneic fetus, respectively. In the testis, immune privilege is "good" as it is necessary for protection of the developing auto-immunogenic germ cells. However, there is also a downside or "bad" part of immune privilege, where pathogens and cancers can take advantage of this privilege and persist in the testis as a sanctuary site. Even worse, the "ugly" of privilege is how re-emerging viruses, such as Ebola and Zika viruses, can establish persistence in the testes and be sexually transmitted even months after they have been cleared from the bloodstream. In this review, we will discuss the delicate balance within the testis that provides immune privilege to protect the germ cells while still allowing for immune function to fight off pathogens and tumors.