Preexposure to CpG protects against the delayed effects of neonatal respiratory syncytial virus infection.
Severe respiratory viral infection in early life is associated with recurrent wheeze and asthma in later childhood. Neonatal immune responses tend to be skewed toward T helper 2 (Th2) responses, which may contribute to the development of a pathogenic recall response to respiratory infection. Since neonatal Th2 skewing can be modified by stimulation with Toll-like receptor (TLR) ligands, we investigated the effect of exposure to CpG oligodeoxynucleotides (TLR9 ligands) prior to neonatal respiratory syncytial virus (RSV) infection in mice. CpG preexposure was protective against enhanced disease during secondary adult RSV challenge, with a reduction in viral load and an increase in Th1 responses. A similar Th1 switch and reduction in disease were observed if CpG was administered in the interval between neonatal infection and challenge. In neonates, CpG pretreatment led to a transient increase in expression of major histocompatibility complex class II (MHCII) and CD80 on CD11c-positive cells and gamma interferon (IFN-γ) production by NK cells after RSV infection, suggesting that the protective effects may be mediated by antigen-presenting cells (APC) and NK cells. We conclude that the adverse effects of early-life respiratory viral infection on later lung health might be mitigated by conditions that promote TLR activation in the infant lung.
Department of Respiratory Medicine, The Centre for Respiratory Infection and the MRC and Asthma UK Centre in Allergic Mechanisms of Asthma, National Heart and Lung Institute, Imperial College London, London, United Kingdom.
Yuko
Y
Yamaguchi
James A
JA
Harker
Belinda
B
Wang
Peter J
PJ
Openshaw
John S
JS
Tregoning
Fiona J
FJ
Culley
D000818:Animals; D000938:Antigen-Presenting Cells / Q000166:cytology; D018899:CpG Islands; D019175:DNA Methylation; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007371:Interferon-gamma / Q000378:metabolism; D007694:Killer Cells, Natural / Q000166:cytology; D051379:Mice; D008807:Mice, Inbred BALB C; D009838:Oligodeoxyribonucleotides; D011247:Pregnancy; D018357:Respiratory Syncytial Virus Infections / Q000235:genetics / Q000276:immunology*; D012136:Respiratory Syncytial Viruses / Q000378:metabolism; D018417:Th1 Cells; D051217:Toll-Like Receptor 9 / Q000378:metabolism
C408982:CPG-oligonucleotide; D009838:Oligodeoxyribonucleotides; D051217:Toll-Like Receptor 9; D007371:Interferon-gamma