The enhancement or prevention of airway hyperresponsiveness during reinfection with respiratory syncytial virus is critically dependent on the age at first infection and IL-13 production

Azzeddine Dakhama, Jung Won Park, Christian Taube, Anthony Joetham, Annette Balhorn, Nobuaki Miyahara, Katsuyuki Takeda, Erwin W. Gelfand

Research output: Contribution to journalArticle

111 Citations (Scopus)

Abstract

Respiratory syncytial virus (RSV) infection in early life is suspected to play a role in the development of postbronchiolitis wheezing and asthma. Reinfection is common at all ages, but factors that determine the development of altered airway function after reinfection are not well understood. This study was conducted in a mouse model to define the role of age in determining the consequences on airway function after reinfection. Mice were infected shortly after birth or at weaning and were reinfected 5 wk later, followed by assessment of airway function, airway inflammation, and lung histopathology. Infection of mice at weaning elicited a protective airway response upon reinfection. In this age group, reinfection resulted in increased airway inflammation, but without development of airway hyperresponsiveness (AHR) or eosinophilia and decreased IL-13 levels. By contrast, neonatal infection failed to protect the airways and resulted in enhanced AHR after reinfection. This secondary response was associated with the development of airway eosinophilia, increased IL-13 levels, and mucus hyperproduction. Both CD4- and CD8-positive T cells were a source of IL-13 in the lung, and inhibition of IL-13 abolished AHR and mucus production in these mice. Inoculation of UV-inactivated virus failed to elicit these divergent responses to reinfection, emphasizing the requirement for active lung infection during initial exposure. Thus, neonatal RSV infection predisposes to the development of airway eosinophilia and enhanced AHR via an IL-13-dependent mechanism during reinfection, whereas infection at a later age protects against the development of these altered airway responses after reinfection.

Original languageEnglish
Pages (from-to)1876-1883
Number of pages8
JournalJournal of Immunology
Volume175
Issue number3
DOIs
Publication statusPublished - 2005 Aug 1

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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