Toll-like receptor 7 function is reduced in adolescents with asthma.
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.
Roponen
M
M
Telethon Institute for Child Health Research, Centre for Child Health Research, University of Western Australia, Perth, Australia.
Yerkovich
S T
ST
Hollams
E
E
Sly
P D
PD
Holt
P G
PG
Upham
J W
JW
D000293:Adolescent; D001249:Asthma / Q000276:immunology*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008297:Male; D051196:Toll-Like Receptor 3 / Q000096:biosynthesis / Q000502:physiology*; D051199:Toll-Like Receptor 7 / Q000096:biosynthesis / Q000502:physiology*
D051196:Toll-Like Receptor 3; D051199:Toll-Like Receptor 7