Human Endometrial Endothelial Cells Generate Distinct Inflammatory and Antiviral Responses to the TLR3 agonist, Poly(I:C) and the TLR8 agonist, viral ssRNA

Abstract

Human endometrial endothelial cell (HEEC) innate immunity remains poorly characterized. Based on their direct contact with the circulation, HEECs are uniquely positioned to be exposed to viral infections. This study evaluated the innate immune response generated by HEECs after exposure to the TLR3 agonist, Poly(I:C) and the TLR8 agonist, viral ssRNA. HEECs were treated with or without Poly(I:C) or ssRNA. Culture supernatants were measured for cytokines by multiplex analysis. RNA was analyzed by qRT-PCR for type I interferons and antiviral factors. Treatment of HEECs with Poly(I:C) rapidly upregulated the secretion of IL-2, IL-6, IL-8, IFN-γ, G-CSF, GM-CSF, MCP-1, MIP-1β, RANTES, and GRO-α after 12hr, while ssRNA treatment induced the slower secretion of IL-6, IL-8, IFN-γ, G-CSF, VEGF, and GRO-α after 24hr. Both viral components induced HEEC IFN-α and IFN-β expression. While treatment with Poly(I:C) induced APOBEC3G and OAS expression, treatment with ssRNA upregulated APOBEC3G and M×A mRNA. Our findings demonstrate that HEECs can differentially sense and respond to viral components by generating distinct inflammatory and antiviral immune responses, indicating that these cells likely play an active role in the immune protection of the uterus toward viral infections.