Enhanced expression of IFI16 and RIG‐I in human third‐trimester placentas following HSV‐1 infection

• Published in: Clinical and experimental immunology Vol. 193; no. 2; pp. 255 - 263
• Main Authors: Jabłońska, A., Studzińska, M., Suski, P., Kalinka, J., Paradowska, E.
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.08.2018; John Wiley and Sons Inc
• Subjects: Adult; Biopsy; Cells, Cultured; Cesarean Section; Cytokines; DEAD Box Protein 58 - genetics; DEAD Box Protein 58 - metabolism; Decidua; Explants; Female; Fetuses; Gestation; Herpes simplex; Herpes Simplex - immunology; Herpesvirus 1, Human - physiology; HSV‐1; Humans; IFI16; Immune response; Immunity, Innate; Immunoassays; Infections; Innate immunity; Interferon; Melanoma; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Organ Culture Techniques; Original; Pattern recognition receptors; Phosphoproteins - genetics; Phosphoproteins - metabolism; Placenta; Placenta - physiology; Polymerase chain reaction; Pregnancy; Pregnancy Complications, Infectious - immunology; Pregnancy Trimester, Third; Protein expression; Proteins; Receptors, Immunologic; Tissues; TLR3 protein; Toll-like receptors; Up-Regulation; pattern-recognition receptors; placenta; HSV-1; cytokines; IFI16
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1111/cei.13143

Summary The innate immune response in the placenta depends on the ability of maternal immune cells and fetal trophoblast cells to detect and eliminate invading pathogens through germline‐encoded pattern recognition receptors (PRRs). In the present study, we analysed the transcripts and protein expression of interferon (IFN)‐inducible protein (IFI)16, melanoma differentiation‐associated protein 5 (MDA5), RIG‐I‐like receptor (RIG‐I) and Toll‐like receptor (TLR)‐3 in third‐trimester human placentas and investigated cytokine profiles generated during herpes simplex type 1 (HSV‐1) infection. Decidual and chorionic villous biopsies (38–42 weeks of gestation) were obtained from healthy women immediately after a caesarean section. The expression of the DDX58 (RIG‐I), IFIH1 (MDA5), IFI16 and TLR3 transcripts was measured using quantitative real‐time polymerase chain reaction (qRT–PCR). Extracellular cytokine and PRRs levels were then quantified by enzyme‐linked immunosorbent assays (ELISAs). All examined PRRs genes, including DDX58, IFIH1, IFI16 and TLR3, were expressed constitutively at the mRNA and protein levels in the placental biopsies. The concentration of the IFI16 protein was increased in HSV‐1‐infected decidual and chorionic villous explants compared to those of mock‐infected tissues (P = 0·029). Higher protein expression levels of RIG‐I in both the maternal and fetal parts of the placenta were found (P = 0·009 and P = 0·004, respectively). In addition, increased production of IFN‐β by HSV‐1‐infected tissues was noticed (P = 0·004 for decidua, P = 0·032 for chorionic villi). No significant differences in the IFN‐α, interleukin (IL)‐6 and IL‐8 levels were found. These results showed that HSV‐1 infection can enhance the expression of IFI16 and RIG‐I proteins in the human term placenta. The protein expression levels of (a) IFI16, (b) TLR3, (c) RIG‐I, and (d) MDA5 in third‐trimester mock‐infected and HSV‐1‐exposed decidual and chorionic villi tissues (n = 8). Data are reported as the mean values ± SEM. Mann‐Whitney two‐tailed test was used to assess statistical significant differences.