Legionella pneumophila Induces IFNβ in Lung Epithelial Cells via IPS-1 and IRF3, Which Also Control Bacterial Replication

• Published in: The Journal of biological chemistry 2006-11, Vol.281 (47), p.36173
• Main Authors: Bastian Opitz, Maya Vinzing, Vincent van Laak, Bernd Schmeck, Guido Heine, Stefan Günther, Robert Preissner, Hortense Slevogt, Philippe Dje N′Guessan, Julia Eitel, Torsten Goldmann, Antje Flieger, Norbert Suttorp, Stefan Hippenstiel
• Format: Article
• Language: English
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M604638200

Legionella pneumophila , a Gram-negative facultative intracellular bacterium, causes severe pneumonia (Legionnaires' disease). Type I interferons (IFNs) were so far associated with antiviral immunity, but recent studies also indicated a role of these cytokines in immune responses against (intracellular) bacteria. Here we show that wild-type L. pneumophila and flagellin-deficient Legionella , but not L. pneumophila lacking a functional type IV secretion system Dot/Icm, or heat-inactivated Legionella induced IFNβ expression in human lung epithelial cells. We found that factor (IRF)-3 and NF-κB-p65 translocated into the nucleus and bound to the IFN β gene enhancer after L. pneumophila infection of lung epithelial cells. RNA interference demonstrated that in addition to IRF3, the caspase recruitment domain (CARD)-containing adapter molecule IPS-1 (interferon-β promoter stimulator 1) is crucial for L. pneumophila -induced IFNβ expression, whereas other CARD-possessing molecules, such as RIG-I (retinoic acid-inducible protein I), MDA5 (melanoma differentiation-associated gene 5), Nod27 (nucleotide-binding oligomerization domain protein 27), and ASC (apoptosis-associated speck-like protein containing a CARD) seemed not to be involved. Finally, bacterial multiplication assays in small interfering RNA-treated cells indicated that IPS-1, IRF3, and IFNβ were essential for the control of intracellular replication of L. pneumophila in lung epithelial cells. In conclusion, we demonstrated a critical role of IPS-1, IRF3, and IFNβ in Legionella infection of lung epithelium.