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Science 339 (6123): 1088-1092

Copyright © 2013 by the American Association for the Advancement of Science

Interferon-{varepsilon} Protects the Female Reproductive Tract from Viral and Bacterial Infection

Ka Yee Fung,1,* Niamh E. Mangan,1,* Helen Cumming,1 Jay C. Horvat,2 Jemma R. Mayall,2 Sebastian A. Stifter,1 Nicole De Weerd,1 Laila C. Roisman,1,3 Jamie Rossjohn,3 Sarah A. Robertson,4 John E. Schjenken,4 Belinda Parker,5,6 Caroline E. Gargett,7,8 Hong P. T. Nguyen,7 Daniel J. Carr,9 Philip M. Hansbro,2 Paul J. Hertzog1,{dagger}

Abstract: The innate immune system senses pathogens through pattern-recognition receptors (PRRs) that signal to induce effector cytokines, such as type I interferons (IFNs). We characterized IFN-{varepsilon} as a type I IFN because it signaled via the Ifnar1 and Ifnar2 receptors to induce IFN-regulated genes. In contrast to other type I IFNs, IFN-{varepsilon} was not induced by known PRR pathways; instead, IFN-{varepsilon} was constitutively expressed by epithelial cells of the female reproductive tract (FRT) and was hormonally regulated. Ifn-{varepsilon}–deficient mice had increased susceptibility to infection of the FRT by the common sexually transmitted infections (STIs) herpes simplex virus 2 and Chlamydia muridarum. Thus, IFN-{varepsilon} is a potent antipathogen and immunoregulatory cytokine that may be important in combating STIs that represent a major global health and socioeconomic burden.

1 Centre for Innate Immunity and Infectious Diseases, Monash Institute of Medical Research, Monash University, Clayton, Victoria, Australia.
2 Centre for Asthma and Respiratory Disease and Hunter Medical Research Institute, The University of Newcastle, Newcastle, New South Wales, Australia.
3 Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia.
4 Robinson Institute and School of Paediatrics and Reproductive Health, University of Adelaide, South Australia, Australia.
5 Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia.
6 Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Australia.
7 The Ritchie Centre, Monash Institute of Medical Research, Monash University, Clayton, Victoria, Australia.
8 Department of Obstetrics and Gynaecology, Monash University, Clayton, Victoria, Australia.
9 Department of Ophthalmology and Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: paul.hertzog{at}

Novel Role for Molecular Transporter Importin 9 in Posttranscriptional Regulation of IFN-{varepsilon} Expression.
T. Matsumiya, F. Xing, M. Ebina, R. Hayakari, T. Imaizumi, H. Yoshida, H. Kikuchi, M. K. Topham, K. Satoh, and D. M. Stafforini (2013)
J. Immunol. 191, 1907-1915
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