Abstract
BackgroundLegionella pneumophila is a facultative intracellular bacterium, capable of replicating within the phagosomes of macrophages and monocytes, but little is known about its interaction with human lung epithelial cells. We investigated the effect of L. pneumophila on the expression of interleukin-8 (IL-8) in human A549 alveolar and NCI-H292 tracheal epithelial cell lines.ResultsInfection of L. pneumophila strain, but not heat-killed strain, resulted in upregulation of IL-8. IL-8 mRNA expression was induced immediately after the infection and its signal became gradually stronger until 24 h after infection. On the other hand, IL-8 expression in A549 cells infected with L. pneumophila lacking a functional type IV secretion system was transient. The IL-8 expression was slightly induced at 16 h and increased at 24 h after infection with flagellin-deficient Legionella. Activation of the IL-8 promoter by L. pneumophila infection occurred through the action of nuclear factor-κB (NF-κB). Transfection of dominant negative mutants of NF-κB-inducing kinase, IκB kinase and IκB inhibited L. pneumophila-mediated activation of IL-8 promoter. Treatment with hsp90 inhibitor suppressed L. pneumophila-induced IL-8 mRNA due to deactivation of NF-κB.ConclusionCollectively, these results suggest that L. pneumophila induces activation of NF-κB through an intracellular signaling pathway that involves NF-κB-inducing kinase and IκB kinase, leading to IL-8 gene transcription, and that hsp90 acts as a crucial regulator in L. pneumophila-induced IL-8 expression, presumably contributing to immune response in L. pneumophila. The presence of flagellin and a type IV secretion system are critical for Legionella to induce IL-8 expression in lung epithelial cells.
Highlights
Legionella pneumophila is a facultative intracellular bacterium, capable of replicating within the phagosomes of macrophages and monocytes, but little is known about its interaction with human lung epithelial cells
The colony forming unit (CFU) per well of AA100jm growing in A549 and NCI-H292 cell cultures began to increase after 24 h and increased timedependently (Figure 1A)
Infection of A549 and NCI-H292 cells by L. pneumophila induces IL-8 expression Monolayers of A549 and NCI-H292 cells were infected with L. pneumophila strain AA100jm for up to 24 h
Summary
Legionella pneumophila is a facultative intracellular bacterium, capable of replicating within the phagosomes of macrophages and monocytes, but little is known about its interaction with human lung epithelial cells. More than 40 species of Legionella are known, the majority of human infections are caused by L. pneumophila, serogroup 1 [1,2]. L. pneumophila can multiply within the mononuclear cells in vivo and in vitro and evades phagosome-lysosome fusion within these cells. It contains an array of important virulence factors including the Dot/Icm type IV secretion system, which is important for bacterial invasion and replication in the host cells [3]. Legionella and other pathogenic organisms, which cause respiratory infection, might well interact with the epithelial cells lining the space
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