IL-22 suppresses HSV-2 replication in human cervical epithelial cells

Cytokine. 2019 Nov:123:154776. doi: 10.1016/j.cyto.2019.154776. Epub 2019 Jul 22.

Abstract

Interleukin (IL)-22, a member of the IL-10 family, plays a role in antiviral immune responses to a number of viral infections. However, it is unclear whether IL-22 is involved in the mucosal immunity against herpes simplex virus 2 (HSV-2) infection in the female reproductive tract (FRT). In this study, we studied whether IL-22 could inhibit HSV-2 infection of human cervical epithelial cells (End1/E6E7 cells). We showed that End1/E6E7 cells express the functional IL-22 receptor complex (IL-22R1 and IL-10R2). When treated with IL-22, End1/E6E7 cells expressed the higher levels of IFN-stimulated genes (ISGs: ISG15, ISG56, OAS-1, OAS-2, and Mx2) than untreated cells. In addition, IL-22-treated cells produced higher levels of the tight junction proteins (ZO-1 and Occludin) than untreated cells. Mechanistically, IL-22 could activate the JAK/STAT signaling pathway by inducing the phosphorylation of STAT1 and STAT3. These observations indicate the potential of IL-22 as an anti-HSV-2 agent in the FRT mucosal innate immunity against HSV-2 infection.

Keywords: HSV-2; Human cervical epithelial cells; IFN-stimulated gene; IL-22; Signal transducers and activators of transcription; Tight junction proteins.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Cervix Uteri / metabolism*
  • Cervix Uteri / pathology
  • Cervix Uteri / virology
  • Epithelial Cells / metabolism*
  • Epithelial Cells / pathology
  • Epithelial Cells / virology
  • Female
  • Herpes Genitalis / metabolism*
  • Herpes Genitalis / pathology
  • Herpesvirus 2, Human / physiology*
  • Humans
  • Interleukin-10 Receptor beta Subunit / metabolism
  • Interleukin-22
  • Interleukins / metabolism*
  • Receptors, Interleukin / metabolism
  • Virus Replication*

Substances

  • IL10RB protein, human
  • Interleukin-10 Receptor beta Subunit
  • Interleukins
  • Receptors, Interleukin
  • interleukin-22 receptor