Previous reports of deficient type I IFN synthesis from circulating cells in asthma have nearly always used RNA viruses such as Newcastle virus and RSV, the influenza virus and HRV. This suggested to us that receptors for viral RNA, and/or their associated adaptor proteins warranted further study. HRV and other RNA viruses replicate in epithelial cells and other structural cells, so cytosolic receptors such as MDA5/RIG-I assume a major role in RNA detection in these cell types. In contrast, viruses do not replicate in pDC and some other migratory leukocyte populations and viral RNA is instead detected by endosomal receptors such as TLR3, TLR7 or TLR8. We previously reported that asthma is associated with abnormal responsiveness to imiquimod, whereas TLR3 function was normal. In the current study we employed GQ: at low concentrations this is specific for TLR7 but at higher concentrations both TLR7 and TLR8 are stimulated. Interestingly, differences between asthmatic and healthy subjects only became apparent at the higher concentration of GQ. TLR3 function was again normal, confirming our previous report. Future studies are now clearly warranted to dissect the relative importance of TLR7 and TLR8 in asthma, and how these receptors interact, particularly given evidence from genetic association studies implicating both TLR7 and TLR8 gene variants in susceptibility to asthma and allergic rhinitis. It is noteworthy that blocking the activity of type I IFNs and depletion of pDC in cultured cells from healthy subjects Fusidate Sodium recapitulated many of the abnormalities observed in the asthmatic donors. This provides strong circumstantial evidence that the altered innate immune response to HRV in allergic asthma can be partly attributed to reduced type-I IFN production and/or pDC dysfunction. There is a need for more detailed studies of the function of purified pDC from people with asthma, though the small numbers of available cells restricts the number of Dehydrocholic acid outcomes that can be evaluated in any one experiment. Interestingly, it seems that asthma is also associated with altered IFN-independent immune pathways as exemplified by reduced expression of several NF-kB family members after HRV exposure.