IFN-ε Is Constitutively Expressed by Cells of the Reproductive Tract and Is Inefficiently Secreted by Fibroblasts and Cell Lines

Type-I interferons (IFNs) form a large family of cytokines that primarily act to control the early development of viral infections. Typical type-I IFN genes, such as those encoding IFN-alpha or IFN-beta are upregulated by viral infection in many cell types. In contrast, the gene encoding IFN-epsilon was reported to be constitutively expressed by cells of the female reproductive tract and to contribute to the protection against vaginal infections with herpes simplex virus 2 and Chlamydia muridarum. Our data confirm the lack of induction of IFN-epsilon expression after viral infection and the constitutive expression of IFN-epsilon by cells of the female but also of the male reproductive organs. Interestingly, when expressed from transfected expression plasmids in 293T, HeLa or Neuro2A cells, the mouse and human IFN-epsilon precursors were inefficiently processed and secretion of IFN-epsilon was minimal. Analysis of chimeric constructs produced between IFN-epsilon and limitin (IFN-zeta) showed that both the signal peptide and the mature moiety of IFN-epsilon contribute to poor processing of the precursor. Immunofluorescent detection of FLAG-tagged IFN-epsilon in transfected cells suggested that IFN-epsilon and chimeric proteins were defective for progression through the secretory pathway. IFN-epsilon did not, however, act intracellularly and impart an antiviral state to producing cells. Given the constitutive expression of IFN-epsilon in specialized cells and the poor processing of IFN-epsilon precursor in fibroblasts and cell lines, we hypothesize that IFN-epsilon secretion may require a co-factor specifically expressed in cells of the reproductive organs, that might secure the system against aberrant release of this IFN.