Pathways:
Toll-like receptor (TLR) signaling pathways
Host Molecules Involved:
TLR-3 is involved in antiviral and inflammatory responses of the innate immunity in response to influenza infections.
Other Molecules:
- Poly ICLC, a synthetic double stranded RNA, polyriboinosinic-poly ribocytidylic acid (Poly IC) stabilized with l-lysine (L) and carboxymethylcellulose (C).
- Poly ICLC and liposome-encapsulated Poly ICLC (LE Poly ICLC) are TLR-3 agonists, potent inducer of interferons and natural killer cells.
Tissues:
Myeloid dendritic cells, respiratory epithelium, and macrophages
Systems:
Host innate immune system
Interactions:
Nucleic acid-based agonists activate toll-like receptor (TLR) signaling pathways.
Mechanisms:
- Influenza viruses inhibit the production of interferons and the immune system’s antiviral mechanisms.
- Poly ICLC and LE Poly ICLC upregulate TLR-3 mRNAs gene expression.
- Pre-treatment of mice with Poly ICLC and LE Poly ICLC protects against highly lethal and seasonal H5N1, H1N1, and H3N2 influenza strains: A/H5N1/chicken/Henan clade 2, A/PR/8/34 [H1N1], and A/Aichi/2 [H3N2].
- Pre-treatment with CpG oligonucleotides (TLR-9 agonist) protects against influenza A/PR/8/34 infection in mice.
- The duration of protective antiviral immunity is up to 3 weeks in mice for LE Poly ICLC, 2 weeks for Poly ICLC.
Effects:
TLR-3 and TLR-9 agonists such as Poly ICLC and LE Poly ICLC may protect against lethal seasonal influenza virus infections.
Reference:
Wong, J. P., Christopher, M. E., et al. (2009) Activation of toll-like receptor signaling pathway for protection against influenza virus infection. Vaccine 27, 3481-3483.
