CpG-oligodeoxynucleotides inhibit RSV-enhanced allergic sensitisation in guinea pigs.
Experimental respiratory syncytial virus (RSV) infection of guinea pigs is associated with enhanced allergic sensitisation to inhaled ovalbumin (OA) and low-level viral persistence in the lungs. Based on the T-helper (Th)1/Th2 paradigm, in which a Th2 shift is characteristic of an allergic response and less effective anti-viral immunity, the effects of immunotherapy with synthetic cytosine phosphate-guanine-oligodeoxynucleotides (CpG-ODN), which are potent Th1 stimuli, on OA sensitisation with and without RSV infection were evaluated. Measurements included quantitative histology for airway inflammation by T-cells and eosinophils, semiquantitative RT-PCR for lung Th1/Th2 balance (interferon (IFN)-gamma/interleukin (IL)-5 mRNA ratios), and serology for circulating titres of OA-specific immunoglobulin (Ig)G1 antibodies. RSV antigens were identified in lung tissue sections by immunohistochemistry. CpG-ODN immunotherapy did not prevent OA sensitisation of guinea pigs; however, in RSV-infected, OA-sensitised animals, CpG-ODN administration was associated with significant reductions of airway T-cells and eosinophils, increased lung IFN-gamma/IL-5 ratios, and decreased OA-specific IgG1 antibody titres to levels observed in uninfected, OA-sensitised animals. Viral antigens were identified in a similar proportion of the lungs of RSV-infected animals, irrespective of CpG-ODN immunisation status. In conclusion, cytosine phosphate-guanine-oligodeoxynucleotides immunotherapy protects guinea pigs against respiratory syncytial virus-enhanced ovalbumin sensitisation and might be a relevant intervention in the context of post-bronchiolitis allergic sensitisation in children.
Tayyari
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James Hogg iCAPTURE Centre for Cardiovascular and Pulmonary Research, St. Paul's Hospital, 1081 Burrard Street, Vancouver, BC, Canada V6Z 1Y6.
Sutton
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TC
Manson
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Hegele
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RG
D000704:Analysis of Variance; D000818:Animals; D018899:CpG Islands / Q000276:immunology*; D005260:Female; D006168:Guinea Pigs; D007074:Immunoglobulin G / Q000097:blood; D007150:Immunohistochemistry; D007249:Inflammation / Q000097:blood; D007371:Interferon-gamma / Q000097:blood; D015848:Interleukin-5 / Q000097:blood; D010047:Ovalbumin / Q000276:immunology; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology*; D012136:Respiratory Syncytial Viruses / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction
D007074:Immunoglobulin G; D015848:Interleukin-5; D007371:Interferon-gamma; D010047:Ovalbumin