Elsevier

Mucosal Immunology

Volume 7, Issue 3, May 2014, Pages 478-488
Mucosal Immunology

Article
Tumor necrosis factor-related apoptosis-inducing ligand translates neonatal respiratory infection into chronic lung disease

https://doi.org/10.1038/mi.2013.65Get rights and content
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Abstract

Respiratory infections in early life can lead to chronic respiratory disease. Chlamydia infections are common causes of respiratory disease, particularly pneumonia in neonates, and are linked to permanent reductions in pulmonary function and the induction of asthma. However, the immune responses that protect against early-life infection and the mechanisms that lead to chronic lung disease are incompletely understood. Here we identify novel roles for tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in promoting Chlamydia respiratory infection-induced pathology in early life, and subsequent chronic lung disease. By infecting TRAIL-deficient neonatal mice and using neutralizing antibodies against this factor and its receptors in wild-type mice, we demonstrate that TRAIL is critical in promoting infection-induced histopathology, inflammation, and mucus hypersecretion, as well as subsequent alveolar enlargement and impaired lung function. This suggests that therapeutic agents that target TRAIL or its receptors may be effective treatments for early-life respiratory infections and associated chronic lung disease.

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Published online: 18 September 2013

SUPPLEMENTARY MATERIAL is linked to the online version of the paper

Supplementary information The online version of this article (doi:10.1038/mi.2013.65) contains supplementary material, which is available to authorized users.