Innate immune response is induced by recognizing pathogen-associated molecular patterns, including double-stranded RNA (dsRNA), and consequently producing immune regulating molecules such as interferon (IFN). In that perspective, treatment with synthetic nucleic acids has helped inducing immune responses. While such molecules have potentials, their in vivo applicability remains a challenge. To address this issue we considered a long (~14 kbp) non-infectious replicon-like dsRNA molecules found in several edible plants. We intend to investigate the immune-modulating capacity of this dsRNA and characterized its potential in immunotherapies.
The plant dsRNA induced IFN response both in vitro and in vivo, in cell lines, primary cells and mouse organs. Upon intranasal inoculation, the IFN induction was dependent on both TLR3/TRIF and MDA5/MAVS, suggesting that the plant dsRNA is a ligand for TLR3 and MDA5. Furthermore, we identified that the main IFN producers are alveolar macrophages. The observed immune-activation in lungs improved antiviral protection against respiratory viruses (influenza A virus and Sendai virus).
Additionally, we investigated the effect of plant dsRNA on progression of B16-F10 melanoma and EAE, which is a mouse model of the multiple sclerosis. Consequently, treatment of plant dsRNA suppressed the growth of B16-F10 melanoma, also reduced incidence and ameliorated EAE symptoms and scores.
This study put forward the immune-modulating capacity of the plant dsRNA and its potential physiological applications. The dsRNA demonstrated strong antiviral, tumor-suppressive capacity and the potential to suppress autoimmune diseases in the CNS.