PLoS Pathogens (Jul 2011)

The role of IL-15 deficiency in the pathogenesis of virus-induced asthma exacerbations.

  • Vasile Laza-Stanca,
  • Simon D Message,
  • Michael R Edwards,
  • Hayley L Parker,
  • Mihnea T Zdrenghea,
  • Tatiana Kebadze,
  • Onn M Kon,
  • Patrick Mallia,
  • Luminita A Stanciu,
  • Sebastian L Johnston

DOI
https://doi.org/10.1371/journal.ppat.1002114
Journal volume & issue
Vol. 7, no. 7
p. e1002114

Abstract

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Rhinovirus infections are the major cause of asthma exacerbations. We hypothesised that IL-15, a cytokine implicated in innate and acquired antiviral immunity, may be deficient in asthma and important in the pathogenesis of asthma exacerbations. We investigated regulation of IL-15 induction by rhinovirus in human macrophages in vitro, IL-15 levels in bronchoalveolar lavage (BAL) fluid and IL-15 induction by rhinovirus in BAL macrophages from asthmatic and control subjects, and related these to outcomes of infection in vivo. Rhinovirus induced IL-15 in macrophages was replication-, NF-κB- and α/β interferon-dependent. BAL macrophage IL-15 induction by rhinovirus was impaired in asthmatics and inversely related to lower respiratory symptom severity during experimental rhinovirus infection. IL-15 levels in BAL fluid were also decreased in asthmatics and inversely related with airway hyperresponsiveness and with virus load during in vivo rhinovirus infection. Deficient IL-15 production in asthma may be important in the pathogenesis of asthma exacerbations.