Legionella pneumophila induces human beta Defensin-3 in pulmonary cells |
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Authors: | Stefanie Scharf Kremena Vardarova Friederike Lang Bernd Schmeck Bastian Opitz Antje Flieger Klaus Heuner Stefan Hippenstiel Norbert Suttorp Philippe D N'Guessan |
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Institution: | 1.Department of Internal Medicine/Infectious Diseases and Pulmonary Medicine, Charité - Universitätsmedizin Berlin, Germany;2.FORSYS Junior Research Group, Systems Biology of Lung Inflammation, Charité-Universitätsmedizin Berlin, Germany;3.FG11 Division of Bacterial infections, Robert Koch-Institut, Wernigerode, Germany;4.P26 Nosocomial Infections of the Elderly, Robert Koch-Institut, Berlin, Germany |
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Abstract: | BackgroundLegionella pneumophila is an important causative agent of severe pneumonia in humans. Human alveolar epithelium and macrophages are effective barriers for inhaled microorganisms and actively participate in the initiation of innate host defense. The beta defensin-3 (hBD-3), an antimicrobial peptide is an important component of the innate immune response of the human lung. Therefore we hypothesize that hBD-3 might be important for immune defense towards L. pneumophila.MethodsWe investigated the effects of L. pneumophila and different TLR agonists on pulmonary cells in regard to hBD-3 expression by ELISA. Furthermore, siRNA-mediated inhibition of TLRs as well as chemical inhibition of potential downstream signaling molecules was used for functional analysis.ResultsL. pneumophila induced release of hBD-3 in pulmonary epithelium and alveolar macrophages. A similar response was observed when epithelial cells were treated with different TLR agonists. Inhibition of TLR2, TLR5, and TLR9 expression led to a decreased hBD-3 expression. Furthermore expression of hBD-3 was mediated through a JNK dependent activation of AP-1 (c-Jun) but appeared to be independent of NF-κB. Additionally, we demonstrate that hBD-3 elicited a strong antimicrobial effect on L. pneumophila replication.ConclusionsTaken together, human pulmonary cells produce hBD-3 upon L. pneumophila infection via a TLR-JNK-AP-1-dependent pathway which may contribute to an efficient innate immune defense. |
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