Dataset Information

IL-17 and TNF-? Are Key Mediators of Moraxella catarrhalis Triggered Exacerbation of Allergic Airway Inflammation.

ABSTRACT: Alterations of the airway microbiome are often associated with pulmonary diseases. For example, detection of the bacterial pathogen Moraxella catarrhalis in the upper airways is linked with an increased risk to develop or exacerbate asthma. However, the mechanisms by which M. catarrhalis augments allergic airway inflammation (AAI) remain unclear. We here characterized the cellular and soluble mediators of M. catarrhalis triggered excacerbation of AAI in wt and IL-17 deficient as well as in animals treated with TNF-? and IL-6 neutralizing antibodies. We compared the type of inflammatory response in M. catarrhalis infected, house dust mite (HDM)-allergic and animals infected with M. catarrhalis at different time points of HDM sensitization. We found that airway infection of mice with M. catarrhalis triggers a strong inflammatory response with massive neutrophilic infiltrates, high amounts of IL-6 and TNF-? and moderate levels of CD4+ T-cell-derived IFN-? and IL-17. If bacterial infection occurred during HDM allergen sensitization, the allergic airway response was exacerbated, particularly by the expansion of Th17?cells and increased TNF-? levels. Neutralization of IL-17 or TNF-? but not IL-6 resulted in accelerated clearance of M. catarrhalis and effectively prevented infection-induced exacerbation of AAI. Taken together, our data demonstrate an essential role for TNF-? and IL-17 in infection-triggered exacerbation of AAI.

SUBMITTER: Alnahas S

PROVIDER: S-EPMC5694487 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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IL-17 and TNF-α Are Key Mediators of Moraxella catarrhalis Triggered Exacerbation of Allergic Airway Inflammation.

Alnahas Safa S Hagner Stefanie S Raifer Hartmann H Kilic Ayse A Gasteiger Georg G Mutters Reinier R Hellhund Anne A Prinz Immo I Pinkenburg Olaf O Visekruna Alexander A Garn Holger H Steinhoff Ulrich U

Frontiers in immunology 20171114

Alterations of the airway microbiome are often associated with pulmonary diseases. For example, detection of the bacterial pathogen Moraxella catarrhalis in the upper airways is linked with an increased risk to develop or exacerbate asthma. However, the mechanisms by which M. catarrhalis augments allergic airway inflammation (AAI) remain unclear. We here characterized the cellular and soluble mediators of M. catarrhalis triggered excacerbation of AAI in wt and IL-17 deficien ...[more]

PMID: 29184554

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Project description:BackgroundViruses are important triggers of asthma exacerbations. They are also detected outside of exacerbation. Alteration of anti-viral response in asthmatic patients has been shown although the mechanisms responsible for this defect remain unclear. The objective of this study was to compare in virus-infected and not-infected allergic asthmatic children, aged 6 to 16 years, admitted to hospital for a severe exacerbation, the innate immune response and especially the expression of pattern recognition receptor (PRR) and their function.MethodsVirus identification was performed both during the exacerbation and at steady state (eight weeks later). Data assessed at both periods included clinical features, anti-viral response and inflammation (in sputum and plasma), and PRR expression/function in blood mononuclear cells.ResultsViruses were identified in 46 out of 72 children (median age 8.9 years) during exacerbation, and among them, in 17 at steady state. IFN-β, IFN-γ and IL-29 levels in sputum and plasma were similar between infected and not infected patients at both times, as well as the expression of TLR3, RIG-I and MDA5 in blood monocytes and dendritic cells. Airway inflammation in infected patients was characterized by significantly higher IL-5 concentration and eosinophil count. Compared to patients only infected at exacerbation, the re-infected children significantly exhibited lower levels of IFN-γ in plasma and sputum at exacerbation associated with modifications in PRR expression and function in blood mononuclear cells. These re-infected patients also presented an airway neutrophilic inflammation at steady state.ConclusionOur results reports in asthmatic children that impaired anti-viral response during virus-induced exacerbation is more pronounced in a subgroup of patients prone to re-infection by virus. This subgroup is characterized by altered PRR function and a different pattern of airway inflammation.Trial registrationThis multicenter prospective study was approved by the regional investigational review board (ref: 08/07).

Dataset Information

IL-17 and TNF-? Are Key Mediators of Moraxella catarrhalis Triggered Exacerbation of Allergic Airway Inflammation.

Publications

IL-17 and TNF-α Are Key Mediators of <i>Moraxella catarrhalis</i> Triggered Exacerbation of Allergic Airway Inflammation.

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