Mechanisms of Legionella pneumophila-induced interleukin-8 expression in human lung epithelial cells

Infection 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.Collectively, 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.Legionella pneumophila causes atypical pneumonia, especially in patients with chronic pulmonary diseases and underlying immunosuppression, and in elderly people. Although more than 40 species of Legionella are known, the majority of human infections are caused by L. pneumophila, particularly serogroup 1 [1,2]. L. pneumophila is a gram-negative, facultative intracellular pathogen of amoeba in natural and man-made aquatic environments. Infection of humans occurs after inhalation of contaminated water aerosol droplets.L. pneumophila can multiply within the mononuclear cells in vivo and in vitro and evades phagosome-lysosome fusio