Anti-viral innate immune responses may be impaired in
asthma, although the mechanisms are not well understood.
Toll-like receptors (TLRs) 7 and 3 are particularly relevant for initiating responses to common respiratory viruses, as they recognise single-stranded
viral RNA and double-stranded
viral RNA, respectively. The aim of the present study was to investigate TLR7 and TLR3 function in 14-yr-old adolescents with
asthma. Blood mononuclear cells obtained from 17 atopic asthmatics, 29 atopic, non-asthmatics and 21 healthy, non-atopic individuals, were stimulated with the TLR7 agonist
imiquimod and the TLR3 agonist
poly I:C. Expression of anti-viral molecules was measured by real-time PCR. Concentrations of
interferon-gamma-inducible
cytokine protein (IP)-10 and
interleukin (IL)-6 were measured by ELISA. TLR7-induced myxovirus resistance
protein A and
2'5' oligoadenylate synthetase mRNA expression and
protein levels of IP-10 were significantly lower in
asthma subjects compared with healthy subjects (p = 0.041, p = 0.003 and p = 0.001 respectively). There was a significant negative correlation between total serum
immunoglobulin E and IP-10 following TLR7 stimulation. However, TLR3-induced responses did not vary with
asthma or atopy.
IL-10 mRNA and
IL-6 protein synthesis were similar in asthmatic and control subjects. In conclusion, TLR7 function is reduced in adolescents with
asthma and this may contribute to susceptibility to respiratory
viral infections.