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Temporal resolutionof two-tracked NF-κBactivationbyLegionellapneumophila Sina BartfeldCäcilia EngelsBianca Bauer2009 год

Temporal resolution of two-tracked NF-κB activation byLegionella pneumophila
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Аннотация: The intracellular pathogen Legionella pneumophila activates the transcription factor NF-kappaB in macrophages and human epithelial cells, contributing to cytokine production and anti-apoptosis. The former is important for the innate immune response to infection, the latter for intracellular replication by securing host cell survival. Here, we demonstrate biphasic activation of NF-kappaB by L. pneumophila in human epithelial cells, using a p65-GFP expressing variant of A549 cells. Early in infection, a strong but transient nuclear translocation of p65 was observed. Only flagellin-deficient (DeltafliA and DeltaflaA) mutants could not induce this first, TLR5 and MyD88-dependent activation. The second p65 translocation event, however, is a long-term activation, independent of flagellin, TLR5 and MyD88, and marked by permanent nuclear localization of p65-GFP without oscillation for 30 h. Persistent p65 translocation also involved degradation of IkappaBalpha and upregulation of anti-apoptotic genes. L. pneumophila mutants lacking a functional Dot/Icm secretion system (DeltadotA; DeltaicmB/dotO), Dot/Icm effectors (DeltasdbA; DeltalubX) and two bacterial effector mutants (DeltaenhC; DeltaptsP) could not induce persistent p65 translocation. Strikingly, all these mutants were deficient in intracellular replication in A549 cells. Our data underline the strong connection between NF-kappaB activation and intracellular replication and hints at an active interference of NF-kappaB signalling by L. pneumophila.
Год издания: 2009
Авторы: Sina Bartfeld, Cäcilia Engels, Bianca Bauer, Philipp Auraß, Antje Flieger, Holger Brüggemann, Thomas F. Meyer
Издательство: Wiley
Источник: Cellular Microbiology
Ключевые слова: Legionella and Acanthamoeba research, Immune Response and Inflammation, Neutrophil, Myeloperoxidase and Oxidative Mechanisms
Другие ссылки: Cellular Microbiology (PDF)
Cellular Microbiology (HTML)
PubMed (HTML)