Current medications have limitations for treating asthma and most people with asthma report reduced quality of life. Several clinical studies are currently trialling TLR7/8 agonists as asthma and allergy treatment, therefore, it is important to understand whether altered TLR7/8 function and genetic variations are common within the asthma population possibly affecting the efficacy of TLR7/8 agonist treatment.
Evidently, asthma is characterised by excessive Th2 responses and susceptibility to respiratory virus infections. Type I interferon protects against virus infections and is important for inhibiting Th2 response but asthma has been associated with low type I interferon production. TLR7 activation stimulates type I interferon production and specific TLR7 variations have been associated with having asthma, therefore, it is possible that certain genetic variations could have an influence on the TLR7 receptor ability to stimulate adequate type I interferon.
We genotyped TLR7 in 215 people and tested their ability to produce type I interferon in response to a TLR7 agonists or human rhinovirus 16. Bblood mononuclear cells were stimulated for 24 hours and interferon-α was measured with ELISA. TLR7 expression levels prior to infection were also measured.
While in this population no genotypes tested associated with having asthma, SNPs upstream of TLR7 associated with both baseline TLR7 expression and rhinovirus induced interferon-α production, though these associations were of borderline statistical significance (P < 0.09). Therefore, certain genetic variations in TLR7 region could have an influence on TLR7 function and its ability to induce interferon-α production.
Whole genome was sequenced in a larger population for further investigation. Those results allow us to examine TLR7/8 role in asthma and antiviral immunity in more detail and provide support for continuing development of TLR7 and TLR8 agonists for asthma treatment. The additional results from whole genome sequencing will be available by the time of the conference.