“Our work provides information on the recognition of single-stranded RNA viruses by the immune system.”

Toll-like receptors (TLRs) are fundamental for the innate immune system to sense invading pathogens by recognizing conserved structures such as lipopolysaccharide, peptidoglycan, flagellin, and unmethylated bacterial CpG-DNA. Our manuscript identified single-stranded RNA as the natural ligand for the two orphan receptors TLR7/TLR8 and explains how the immune system recognizes single-stranded RNA viruses. It is also interesting to realize that two other groups, that of Caetano Reis e Sousa at the Imperial Cancer Research Fund (ICRF) in London and Richard Flavell of the Howard Hughes Medical Institute at Yale University in New Haven simultaneously published results leading to the same conclusion.

Our work provides information on the recognition of single-stranded RNA viruses by the immune system. The identification of single-stranded RNA via TLR7 and TLR8 has an interesting potential for the development of novel methods of immunization for vaccine design using RNA as adjuvant.

For a long time, it was unclear how the innate immune system recognizes invading pathogens and leads to the activation of immune cells fighting the infection. The Toll-like receptors have recently been identified as key molecules in sensing pathogens and activating immune cells. This activation leads to the generation of an adaptive immune response resulting in the eradication of pathogens. Our work has now identified the Toll-like receptors 7 and 8 as sensors for single-stranded RNA and explains how the innate immune system recognizes and fights against single-stranded viruses such as the influenza virus.

Innate immunity has been a focus of my research for years. The identification of unmethylated bacterial CpG-deoxyribonucleic acid (CpG-DNA) as natural ligand for TLR9 prompted us to identify the ligands for TLR7 and 8. Since these receptors share homology with TLR9, we investigated ribonucleic acid (RNA) as a possible stimulus.