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IL-6 Deficiency Exacerbates Allergic Asthma and Abrogates the Protective Effect of Allergic Inflammation against
- Source :
- J Immunol
- Publication Year :
- 2019
-
Abstract
- Allergic asthma (AA) is characterized as a Th2-biased airway inflammation that can develop lung inflammation and remodeling of the respiratory tract. Streptococcus pneumoniae is a major respiratory pathogen, causing noninvasive (otitis media and pneumonia) and invasive diseases (sepsis) in humans. We sought to determine the role of IL-6 in the regulation of lung inflammation in murine AA caused by Aspergillus fumigatus as well as its consequence on the regulation of airway barrier integrity and S. pneumoniae disease. In an AA model, IL-6 deficiency led to increased lung inflammation, eosinophil recruitment, tissue pathology, and collagen deposition. Additionally, IL-6–deficient asthmatic mice exhibited reduced goblet cell hyperplasia and increased TGF-β production. These key changes in the lungs of IL-6–deficient asthmatic mice resulted in dysregulated tight junction proteins and increased lung permeability. Whereas the host response to AA protected against S. pneumoniae lung disease, the IL-6 deficiency abrogated the protective effect of allergic inflammation against S. pneumoniae pathogenesis. Consistent with in vivo data, IL-6 knockdown by small interfering RNA or the blockade of IL-6R signaling exacerbated the TGF-β–induced dysregulation of tight junction proteins, E-cadherin and N-cadherin expression, and STAT3 phosphorylation in MLE-12 epithelial cells. Our findings demonstrate a previously unrecognized role of host IL-6 response in the regulation of lung inflammation during AA and the control of S. pneumoniae bacterial disease. A better understanding of the interactions between lung inflammation and barrier framework could lead to the development of therapies to control asthma inflammation and preserve barrier integrity.
- Subjects :
- Mice, Knockout
Hyperplasia
Infectious Disease and Host Response
Interleukin-6
Pneumonia
Respiratory Mucosa
respiratory system
Pneumonia, Pneumococcal
Asthma
respiratory tract diseases
Tight Junctions
Disease Models, Animal
Mice
Streptococcus pneumoniae
Transforming Growth Factor beta
Hypersensitivity
Animals
Humans
Goblet Cells
RNA, Small Interfering
Cells, Cultured
Disease Resistance
Signal Transduction
Subjects
Details
- ISSN :
- 15506606
- Volume :
- 205
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Accession number :
- edsair.pmid..........f829178d77ae5a844daa8104eb807329