Insight into the expression of RIG-I-like receptors in human third trimester placentas following ex vivo cytomegalovirus or vesicular stomatitis virus infection

Abstract

A viral infection is detected through germline-encoded pattern-recognition receptors (PRRs) leading to the production of interferons (IFNs) and proinflammatory cytokines. The objective of this study was to investigate the expression of retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs) in response to viral infection and the selected cytokine responses in the human term placenta. Placental villi and decidual explants were infected with human cytomegalovirus (CMV) or vesicular stomatitis virus (VSV) and cultured ex vivo to study viral infection. To evaluate DDX58 (RIG-I), IFIH1 (MDA5), and DHX58 (LGP2) expression, quantitative real-time PCR (qRT-PCR) was used. The expression of RLRs was detected by Western blotting. Cytokine and chemokine production, as well as RLR protein levels, were quantified using ELISA. The increased expression of both RIG-I and MDA5 and the enhanced secretion of IFN-ß were observed in response to VSV infection compared to mock-infected tissues. CMV infection resulted in higher transcript levels of DDX58 and IFIH1, while no changes in the cytokine production were observed. Our results indicate that RIG-I and MDA5 are specifically expressed in chorionic villi and deciduae in response to VSV infection. These findings suggest that RLRs may play a key role in pathogen recognition and the immune response against intrauterine viral transmission.