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Pulmonary immunity during respiratory infections in early life and the development of severe asthma
- Source :
- Annals of the American Thoracic Society. 11
- Publication Year :
- 2014
-
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 apoptosis-inducing 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.
- Subjects :
- Pulmonary and Respiratory Medicine
Population
Respiratory physiology
Disease
medicine.disease_cause
Severity of Illness Index
Mice
Medicine
Animals
Humans
Respiratory system
education
Lung
Respiratory Tract Infections
Asthma
education.field_of_study
Immunity, Cellular
business.industry
Age Factors
respiratory system
Allergens
medicine.disease
Mucus
respiratory tract diseases
Interleukin 13
Immunology
Cytokines
Rhinovirus
business
Subjects
Details
- ISSN :
- 23256621
- Volume :
- 11
- Database :
- OpenAIRE
- Journal :
- Annals of the American Thoracic Society
- Accession number :
- edsair.doi.dedup.....f98a1994a876d7c5d1aeec9915f367ed