Interferon-ε Protects the Female Reproductive Tract from Viral and Bacterial Infection

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-ε as a type I IFN because it signaled via the Ifnar1 and Ifnar2 receptors to induce IFN-regulated genes. In contras...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 2013-03, Vol.339 (6123), p.1088-1092
Main Authors: Fung, Ka Yee, Mangan, Niamh E., Cumming, Helen, Horvat, Jay C., Mayall, Jemma R., Stifter, Sebastian A., De Weerd, Nicole, Roisman, Laila C., Rossjohn, Jamie, Robertson, Sarah A., Schjenken, John E., Parker, Belinda, Gargett, Caroline E., Nguyen, Hong P. T., Carr, Daniel J., Hansbro, Philip M., Hertzog, Paul J.
Format: Article
Language:English
Subjects:
Animals
Bacteria
Cell Line
Cell lines
Chlamydia
Chlamydia Infections - genetics
Chlamydia Infections - immunology
Chlamydia muridarum
Cytokines
Epithelial cells
Estrogens - administration & dosage
Estrogens - immunology
Female
Females
Genetics
HEK293 Cells
Herpes Genitalis - genetics
Herpes Genitalis - immunology
Herpes simplex virus 2
Herpesvirus 2, Human
Human
Human herpesvirus 2
Humans
Infections
Interferons - genetics
Interferons - immunology
Ligands
Medical research
Mice
Mice, Inbred C57BL
Oligodeoxyribonucleotides - immunology
Pathogens
Poly dA-dT - immunology
Poly I-C - immunology
Receptors
Research universities
Tissue samples
Toll-Like Receptors - immunology
Uterus - immunology
Vagina - immunology
Vagina - microbiology
Vagina - virology
Viruses
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Description
Summary: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-ε 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-ε was not induced by known PRR pathways; instead, IFN-ε was constitutively expressed by epithelial cells of the female reproductive tract (FRT) and was hormonally regulated. Ifn-ε-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-ε is a potent antipathogen and immunoregulatory cytokine that may be important in combating STIs that represent a major global health and socioeconomic burden.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.1233321