IL-22 suppresses HSV-2 replication in human cervical epithelial cells. (November 2019)

• Record Type: Journal Article
• Authors: Xu, Xi-Qiu; Liu, Yu; Zhang, Biao; Liu, Hang; Shao, Dan-Dan; Liu, Jin-Biao; Wang, Xu; Zhou, Li-Na; Hu, Wen-Hui; Ho, Wen-Zhe
• Is Part Of: Cytokine. Volume 123(2019)
• Publication Date: 2019-11
• Subjects: Human cervical epithelial cells -- IL-22 -- IFN-stimulated gene -- Signal transducers and activators of transcription -- Tight junction proteins -- HSV-2; IL-22 Interleukin 22 -- IL-TIF IL-10-related T cell-derived inducible factor -- HSV-2 Herpes simplex virus 2 -- HPV16 Human papillomavirus type 16 -- HIV Human immunodeficiency virus -- HBV Hepatitis B virus -- FRT Female reproductive tract -- HCEs Human cervical epithelial cells -- DMEM Dulbecco's modified eagle medium -- FBS Fetal bovine serum -- PBS Phosphate-buffered saline -- JAK Janus kinases -- STAT Signal transducers and activators of transcription -- ISG IFN-stimulated gene -- TJs Tight junction proteins -- MOI Multiplicity of infection -- PFU Plaque forming unit -- IE genes Immediate early genes -- E genes Early genes -- L genes Late genes; Cytokines -- Periodicals; 571.844
• DOI: 10.1016/j.cyto.2019.154776
• Languages: English
• ISSNs: 1043-4666

Abstract

Highlights: Human cervical epithelial cells (HCEs) express the functional IL-22 receptor. IL-22 inhibits HSV-2 replication in HCEs. IL-22 induces the expression of ISGs and the tight junction proteins in HCEs. IL-22 has potential as a therapeutic agent to inhibit HSV-2 infection. 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.