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-α or IFN-β are upregulated by viral infection in many cell types. In contrast, the gene encoding IFN-ε 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-ε expression after viral infection and the constitutive expression of IFN-ε 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-ε precursors were inefficiently processed and secretion of IFN-ε was minimal. Analysis of chimeric constructs produced between IFN-ε and limitin (IFN-ζ) showed that both the signal peptide and the mature moiety of IFN-ε contribute to poor processing of the precursor. Immunofluorescent detection of FLAG-tagged IFN-ε in transfected cells suggested that IFN-ε and chimeric proteins were defective for progression through the secretory pathway. IFN-ε did not, however, act intracellularly and impart an antiviral state to producing cells. Given the constitutive expression of IFN-ε in specialized cells and the poor processing of IFN-ε precursor in fibroblasts and cell lines, we hypothesize that IFN-ε 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.
Université catholique de Louvain, de Duve Institute, Brussels, Belgium.
Pascale
P
Hermant
Cédric
C
Francius
Frédéric
F
Clotman
Thomas
T
Michiels
D000818:Animals; D045744:Cell Line, Tumor; D004622:Embryo, Mammalian; D005260:Female; D005347:Fibroblasts / Q000378:metabolism* / Q000821:virology; D015870:Gene Expression; D006801:Humans; D007372:Interferons / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008574:Mengovirus / Q000254:growth & development; D051379:Mice; D008810:Mice, Inbred C57BL; D010053:Ovary / Q000166:cytology / Q000378:metabolism* / Q000821:virology; D061251:Primary Cell Culture; D013737:Testis / Q000166:cytology / Q000378:metabolism* / Q000821:virology; D014599:Uterus / Q000166:cytology / Q000378:metabolism* / Q000821:virology
C578688:interferon-epsilon, mouse; D007372:Interferons