Analyses of the IL-6 signaling pathway in HSV-1-infected dendritic cells and characterization of HSV-1-derived L-particles
The human organism is protected from the continuous threat of pathogens by the immune system. Dendritic cells (DCs) are the most potent antigen presenting cells and play a pivotal role in the induction of protective adaptive immune responses against such pathogens. Thus, DCs represent an interesting target for virus-induced immune-evasion strategies. In this respect, herpes simplex virus type 1 (HSV-1) has evolved several immune evasion mechanism in order to hamper the induction of a potent antiviral immune response by interfering with DC biology.
Since the IL-6 signaling pathway is important for the induction of anti-viral immune responses, this pathway is frequently targeted by specific viruses, including Enterovirus 71 and influenza A virus. To investigate, if and how also herpesviruses interfere with the IL-6 signaling pathway, we analyzed the expression of IL6Rα and STAT3 during HSV-1 infection.
Thereby we found out that HSV-1 modulates the expression levels of IL6Rα as well as STAT3 of directly-infected mDCs. Regarding IL6Rα, not only directly-infected but also uninfected “bystander” mDCs displayed reduced IL6Rα protein and mRNA expression levels, however, in a timely-delayed manner. Our work demonstrates that HSV-1-derived L-particles transport viral proteins to uninfected “bystander” DCs, to induce the downmodulation of functionally important proteins, such as IL6Rα, and thereby hamper DC mediated antiviral immune responses.
