Targeting the toll-like receptor 7 pathway in asthma: a potential immunomodulatory approach?

Abstract

In allergic airways, as in asthma, inflammation and impaired functioning of toll-like receptor 7 (TLR7) has been found. The augmentation of this receptor with agonist compounds resulted in bronchodilation and a switch of the TH2 inflammatory pattern, specific for allergic conditions, to TH1 inflammation, characterised by an increased production of interferon-γ. This was a preclinical study evaluating the effects of two TLR7 agonists, imiquimod and resiquimod, on the isolated guinea pig trachea. The TLR7-related downstream signalling pathways were also assessed. Both TLR7 agonists were shown to reduce serotonin-induced bronchoconstriction, which is possibly exerted via the p38MAPK and NF-κB pathways. Therapeutic targeting of TLR7 with specific agonists might represent a promising immunomodulatory approach in asthma, especially if systemic exposure is minimised with inhaled formulations.