Legionella pneumophila Induces IFNβ in Lung Epithelial Cells via IPS-1 and IRF3, Which Also Control Bacterial Replication
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 (intra...
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Published in | The Journal of biological chemistry Vol. 281; no. 47; p. 36173 |
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Main Authors | , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
American Society for Biochemistry and Molecular Biology
24.11.2006
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Online Access | Get full text |
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Summary: | 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. |
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ISSN: | 0021-9258 1083-351X |
DOI: | 10.1074/jbc.M604638200 |