TY - JOUR
T1 - Antiviral IFN-γ responses of monocytes at birth predict respiratory tract illness in the first year of life
AU - Sumino, Kaharu
AU - Tucker, Jennifer
AU - Shahab, Muhammad
AU - Jaffee, Katy F.
AU - Visness, Cynthia M.
AU - Gern, James E.
AU - Bloomberg, Gordon R.
AU - Holtzman, Michael J.
N1 - Funding Information:
Supported by grants from the National Institutes of Health (National Institute of Allergy and Infectious Diseases and National Heart, Lung, and Blood Institute) .
Funding Information:
Disclosure of potential conflict of interest: K. Sumino has received research support from the National Institutes of Health (NIH) . J. E. Gern is on the scientific advisory board for and owns stock options in 3V Biosciences; has consulted for Centocor, Boeheringer Ingelheim, GlaxoSmithKline, Biota, MedImmune, and Theraclone; and has received research support from AstraZeneca . G. R. Bloomberg has received research support from the NIH/National Institute of Allergy and Infectious Diseases . M. J. Holtzman has consulted for and received research support from Hoffman–La Roche and Forest Laboratories . The rest of the authors declare that they have no relevant conflicts of interest.
PY - 2012/5
Y1 - 2012/5
N2 - 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 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 = -0.42, P <.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.
AB - 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 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 = -0.42, P <.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.
KW - Viral respiratory tract infection
KW - allergic disease
KW - asthma
KW - cord blood monocytes
KW - infants
UR - http://www.scopus.com/inward/record.url?scp=84860492288&partnerID=8YFLogxK
U2 - 10.1016/j.jaci.2012.02.033
DO - 10.1016/j.jaci.2012.02.033
M3 - Article
C2 - 22460071
AN - SCOPUS:84860492288
SN - 0091-6749
VL - 129
SP - 1267-1273.e1
JO - Journal of Allergy and Clinical Immunology
JF - Journal of Allergy and Clinical Immunology
IS - 5
ER -