Ovalbumin sensitization changes the inflammatory response to subsequent parainfluenza infection: Eosinophils mediate airway hyperresponsiveness, M2 muscarinic receptor dysfunction, and antiviral effects

Darryl J. Adamko, Bethany L. Yost, Gerald J. Gleich, Allison D. Fryer, David B. Jacoby

Research output: Contribution to journalArticle

133 Scopus citations

Abstract

Asthma exacerbations, many of which are virus induced, are associated with airway eosinophilia. This may reflect altered inflammatory response to viruses in atopic individuals. Inhibitory M2 muscarinic receptors (M2Rs) on the airway parasympathetic nerves limit acetylcholine release. Both viral infection and inhalational antigen challenge cause M2R dysfunction, leading to airway hyperresponsiveness. In antigen-challenged, but not virus-infected guinea pigs, M2R dysfunction is due to blockade of the receptors by the endogenous antagonist eosinophil major basic protein (MBP). We hypothesized that sensitization to a nonviral antigen before viral infection alters the inflammatory response to viral infection, so that M2R dysfunction and hyperreactivity are eosinophil mediated. Guinea pigs were sensitized to ovalbumin intraperitoneally, and 3 wk later were infected with parainfluenza, in sensitized, but not in nonsensitized animals, virus-induced hyperresponsiveness and M2R dysfunction were blocked by depletion of eosinophils with antibody to interleukin (IL)-5 or treatment with antibody to MBP. An additional and unexpected finding was that sensitization to ovalbumin caused a marked (80%) reduction in the viral content of the lungs. This was reversed by the antibody to IL-5, implicating a role for eosinophils in viral immunity.

Original languageEnglish (US)
Pages (from-to)1465-1477
Number of pages13
JournalJournal of Experimental Medicine
Volume190
Issue number10
DOIs
StatePublished - Nov 15 1999
Externally publishedYes

Keywords

  • Antigen challenge
  • Eosinophils
  • Muscarinic receptors
  • Parainfluenza virus
  • Viral immunity

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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