Toll-like receptor 9 dependent interferon-α release is impaired in severe asthma but is not associated with exacerbation frequency.

Patients with asthma and chronic obstructive pulmonary disease (COPD) are susceptible to exacerbations, often caused by microbial pathogens. We hypothesised that intracellular Toll-like receptor (TLR) function in blood mononuclear cells (PBMCs) from these subjects would be impaired and that this impairment is related to exacerbation frequency. PBMCs stimulated with a TLR-9 agonist (but not TLR-3 or 7/8) produced significantly less IFN-α in asthma (26 [3-696]pg/ml) compared to control (943 [164-1651]) and COPD (597 [127-1186]) subjects (p = 0.0019) but this was not related to the number of exacerbations per year in asthma or COPD. In COPD, IFN-α levels were related to KCO (% predicted) in COPD (r = -0.41, p = 0.01). IFN-α was derived from plasmacytoid dendritic cells (pDCs) and their frequency was lower in asthma compared to control subjects (control 0.48% [0.33-0.64] versus asthma 0.29% [0.13-0.34], p = 0.019) whereas pDC function per se was not significantly impaired between groups. The mechanism underlying reduced IFN-α production and the clinical consequences in severe asthma remains to be established.