Poster Presentation Lorne Infection and Immunity 2022

Anti-viral defences in the male reproductive tract: Expression and localisation of the novel type I interferon epsilon (#227)

Rukmali Wijayarathna 1 2 , Eveline de Geus 2 3 , Rajini Sreenivasan 4 , Rosemary Genovese 4 , Paul Hertzog 2 3 , Mark P Hedger 1 2
  1. Centre For Reproductive Health, Hudson Institute of Medical Research, Melbourne, Victoria, Australia
  2. Dept. of Molecular and Translational Sciences, School of Clinical Sciences, Monash University, Melbourne, Victoria, Australia
  3. Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Melbourne, Victoria, Australia
  4. Hudson Institute of Medical Research, Clayton, Victoria, Australia

Interferon epsilon (Ifnɛ), a novel type-I interferon constitutively expressed in female reproductive epithelia, protects female mice against sexually transmitted viruses. Production, cellular localization, and functions of Ifnɛ in the male reproductive tract have not been studied previously. Since many viruses, including HIV, HSV2, HepB, mumps, Zika, and SARS disrupt male reproductive function, investigation of this potent anti-viral agent in the male was warranted. 

Expression and localization of Ifnɛ in the male reproductive tract was studied by indirect immunofluorescence and qRT-PCR in 25 and 56 day old wild-type mice relative to Ifnɛ-/- mice (n = 8/genotype). Wild-type testes between days 5 and 180 were examined to determine Ifnɛ expression during postnatal development. Cellular sites of production were determined in individual testicular cell types isolated from 44 day old mice using Percoll gradient centrifugation, centrifugal elutriation and lectin-adherence.

Ifnɛ was differentially expressed within the male reproductive tract. Expression was very high in the testis, absent in the epididymis, and low in the vas deferens at both day 25 (prior to the completion of sperm production), and day 56 (mature spermatogenesis). Testicular Ifnɛ first appeared between day 20 and 25, and was expressed in meiotic and post meiotic germ cells, and in interstitial cells, particularly macrophages. Interferon-stimulated genes (ISG), such as Isg15, Irf7, and Oasl2, displayed low expression in the testis, and gradually increased towards the cauda epididymis and vas deferens, in parallel with other type-I interferons, such as Ifnb1.  Unlike in the female, Ifnε deficiency did not reduce ISG expression within the male reproductive tract.

Constitutive expression of Ifnɛ in the mature testis, the region most prone to viral infections within the male reproductive tract, suggests a crucial role for Ifnɛ in testicular innate immunoregulation and protection, whereas other type-I interferons may play a more significant protective role in the distal epididymis.