Pulmonary immunity during respiratory infections in early life and the development of severe asthma

Philip M. Hansbro, Malcolm R. Starkey, Joerg Mattes, Jay C. Horvat

Research output: Contribution to journalArticleResearchpeer-review

25 Citations (Scopus)

Abstract

Asthma affects 10% of the population in Westernized countries, being most common in children. It is a heterogeneous condition characterized by chronic allergic airway inflammation, mucus hypersecretion, and airway hyperresponsiveness (AHR) to normally innocuous antigens. Combination therapies with inhaled corticosteroids and bronchodilators effectively manage mild to moderate asthma, but there are no cures, and patients with severe asthma do not respond to these treatments. The inception of asthma is linked to respiratory viral (respiratory syncytial virus, rhinovirus) and bacterial (Chlamydia, Mycoplasma) infections. The examination of mouse models of early-life infections and allergic airway disease (AAD) provides valuable insights into the mechanisms of disease inception that may lead to the development of more effective therapeutics. For example, early-life, but not adult, Chlamydia respiratory infections in mice permanently modify immunity and lung physiology. This increases the severity of AAD by promoting IL-13 expression, mucus hypersecretion, and AHR. We have identified novel roles for tumor necrosis factor-related apoptosisinducing ligand (TRAIL) and IL-13 in promoting infection-induced pathology in early life and subsequent chronic lung disease. Genetic deletion of TRAIL or IL-13 variously protected against neonatal infection-induced inflammation, mucus hypersecretion, altered lung structure, AHR, and impaired lung function. Therapeutic neutralization of these factors prevented infection-induced severe AAD. Other novel mechanisms and avenues for intervention are also being explored. Such studies indicate the immunological mechanisms that may underpin the association between early-life respiratory infections and the development of more severe asthma and may facilitate the development of tailored preventions and treatments.

Original languageEnglish
Pages (from-to)S297-S302
Number of pages6
JournalAnnals of the American Thoracic Society
Volume11
DOIs
Publication statusPublished - 1 Dec 2014
Externally publishedYes

Keywords

  • Asthma
  • Chlamydia
  • Early life
  • IL-13
  • Tumor necrosis factor-related apoptosis-inducing ligand

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