IL-17 and TNF-α Are Key Mediators of Moraxella catarrhalis Triggered Exacerbation of Allergic Airway Inflammation
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IL-17 and TNF-α Are Key Mediators of Moraxella catarrhalis Triggered Exacerbation of Allergic Airway Inflammation. / Alnahas, Safa; Hagner, Stefanie; Raifer, Hartmann; Kilic, Ayse; Gasteiger, Georg; Mutters, Reinier; Hellhund, Anne; Prinz, Immo; Pinkenburg, Olaf; Visekruna, Alexander; Garn, Holger; Steinhoff, Ulrich.
In: FRONT IMMUNOL, Vol. 8, 14.11.2017, p. 1562.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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T1 - IL-17 and TNF-α Are Key Mediators of Moraxella catarrhalis Triggered Exacerbation of Allergic Airway Inflammation
AU - Alnahas, Safa
AU - Hagner, Stefanie
AU - Raifer, Hartmann
AU - Kilic, Ayse
AU - Gasteiger, Georg
AU - Mutters, Reinier
AU - Hellhund, Anne
AU - Prinz, Immo
AU - Pinkenburg, Olaf
AU - Visekruna, Alexander
AU - Garn, Holger
AU - Steinhoff, Ulrich
PY - 2017/11/14
Y1 - 2017/11/14
N2 - 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-α 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-α and moderate levels of CD4+ T-cell-derived IFN-γ 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-α levels. Neutralization of IL-17 or TNF-α 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-α and IL-17 in infection-triggered exacerbation of AAI.
AB - 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-α 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-α and moderate levels of CD4+ T-cell-derived IFN-γ 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-α levels. Neutralization of IL-17 or TNF-α 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-α and IL-17 in infection-triggered exacerbation of AAI.
U2 - 10.3389/fimmu.2017.01562
DO - 10.3389/fimmu.2017.01562
M3 - SCORING: Journal article
C2 - 29184554
VL - 8
SP - 1562
JO - FRONT IMMUNOL
JF - FRONT IMMUNOL
SN - 1664-3224
ER -