Infants experiencing severe respiratory syncytial virus (RSV) bronchiolitis have an increased

Infants experiencing severe respiratory syncytial virus (RSV) bronchiolitis have an increased frequency of wheeze and asthma in later childhood. might reduce subsequent respiratory morbidity in later childhood. and speculated CK-1827452 manufacturer that this was due to suppression of T cell responses in the environment of the neonatal lung (27). Our data suggest that such differences in neonatal immune responses can have long-lasting consequences for the host. We suggest that a weaker Th1 response during primary infection may allow the development of stronger Th2 responses to rechallenge later in life, so explaining the enhanced disease, lymphocyte, and granulocyte recruitment in adult CK-1827452 manufacturer reinfection. It is currently unclear whether the Th2 bias in the neonatal immune system is due to the T cells, their environment, or both. For example, neonatal dendritic cells are deficient in IL-12 production, an important factor in the differentiation of Th1 cells (28) and respiratory tract dendritic cells are less numerous and mature in the neonatal than in the adult lung (29). The intrinsic properties of the T cell may differ in neonates. For example, reduced IFN- production by neonatal CD4+ T cells may be explained by differential patterns of methylation of the IFN- promoter (30). In conclusion, our results show that this timing of RSV contamination in newborn mice is usually a crucial factor in determining the outcome of reinfection in adulthood and that early neonatal contamination is associated with long lasting bias toward Th2 responses to rechallenge. Therefore, delaying RSV contamination might avoid the delayed consequences of bronchiolitis, possibly reducing the frequency of respiratory symptoms in EFNA3 later childhood. These novel findings highlight the importance of early life infections in determining subsequent patterns of disease and suggest that efforts should be directed toward delaying RSV disease until children are more immunologically mature. Acknowledgments We wish to thank Professor C.-A. Siegrist and members of the CK-1827452 manufacturer Department of WHO Centre of Vaccinology and Neonatal Immunology, Geneva, Switzerland for guidance; Dr. S. Riffault for her assistance and Professor B. Askonas for fruitful discussions. The PCR for RSV was devised by Dr. C. Ward, GlaxoSmithKline, UK, who kindly provided the standard plasmid. This work was funded by the European Union Neovac Consortium and Wellcome Trust Programme 054797..