Antiviral IFN-纬 responses of monocytes at birth predict respiratory tract illness in the first year of life

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• 作者：Kaharu Sumino ; MD ; MPH^a ; Jennifer Tucker ; MS^a ; Muhammad Shahab ; MD^a ; Katy F. Jaffee ; MS^d ; Cynthia M. Visness ; PhD^d ; James E. Gern ; MD^e ; Gordon R. Bloomberg ; MD^b ; Michael J. Holtzman ; MD^a ; ^c ; ^{holtzmanm@wustl.edu}
• 关键词：Viral respiratory tract infection ; cord blood monocytes ; infants ; asthma ; allergic disease
• 刊名：Journal of Allergy and Clinical Immunology
• 出版年：2012
• 期刊代码：158_00916749
• 类别：med
• 出版时间：May, 2012
• 卷：129
• 期：5
• 页码：1267-1273.e1
• 文件大小：321 K

摘要

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Background

Viral respiratory tract infections are the leading cause of acute illness during infancy and are closely linked to chronic inflammatory airway diseases later in life. However, the determinants of susceptibility to acute respiratory tract infections still need to be defined.

Objective

We investigated whether the individual variation in antiviral response at birth determines the risk for acute respiratory tract illness in the first year of life.

Methods

We studied 82 children who were enrolled in a birth cohort study of inner-city children with at least 1 parent with allergy or asthma. We cultured cord blood monocytes and assessed IFNG and CCL5 mRNA production at 24 hours after inoculation with respiratory syncytial virus. We also monitored the frequency of acute respiratory tract illness at 3-month intervals and analyzed nasal lavage samples for respiratory tract viruses at the time of illness during the first聽year.

Results

Respiratory tract infection was reported for 88%of subjects, and respiratory tract viruses were recovered in 74%of symptomatic children. We observed a wide range of antiviral responses in cord blood monocytes across the population. Furthermore, a decrease in production of IFNG (but not CCL5) mRNA in response to respiratory syncytial virus infection of monocytes was associated with a significant increase in the frequency of upper respiratory tract infections (r聽= 鈭?.42, P聽< .001) and the prevalence of ear and sinus infections, pneumonias, and respiratory-related hospitalizations.

Conclusion

Individual variations in the innate immune response to respiratory tract viruses are detectable even at birth, and these differences predict the susceptibility to acute respiratory tract illness during the first year of life.