Novel role of proton-secreting epithelial cells in sperm maturation and mucosal immunity

Epithelial cells are immune sensors and mediators that constitute the first line of defense against infections. Using the epididymis, a model for studying tubular organs, we uncovered a novel and unexpected role for professional proton secreting “clear cells” in sperm maturation and immune defense. The epididymal epithelium participates in the maturation of spermatozoa, via the establishment of an acidic milieu, and transfer of proteins to sperm cells, a poorly characterized process. We show that proton-secreting “clear cells” express mRNA transcripts and proteins that are acquired by maturing sperm, and that they establish close interactions with luminal spermatozoa via newly described “nanotubes”. Mechanistic studies show that injection of bacterial antigens in vivo induces chemokine expression in clear cells, followed by macrophage recruitment into the organ. Injection of an inflammatory intermediate mediator (IFN-gamma) increased Cxcl10 expression in clear cells, revealing their participation as sensors and mediators of inflammation. The functional diversity adopted by clear cells might represent a generalized phenomenon by which similar epithelial cells decode signals, communicate with neighbors, and mediate mucosal immunity, depending on their precise location within an organ.