title: Molecular characterization of Legionella pneumophila-induced interleukin-8 expression in T cells.
abstract: BACKGROUND
  Legionella pneumophila is the causative agent of human Legionnaire's disease. During infection, the bacterium invades macrophages and lung epithelial cells, and replicates intracellularly. However, little is known about its interaction with T cells. We investigated the ability of L. pneumophila to infect and stimulate the production of interleukin-8 (IL-8) in T cells. The objective of this study was to assess whether L. pneumophila interferes with the immune system by interacting and infecting T cells.
  
  
  RESULTS
  Wild-type L. pneumophila and flagellin-deficient Legionella, but not L. pneumophila lacking a functional type IV secretion system Dot/Icm, replicated in T cells. On the other hand, wild-type L. pneumophila and Dot/Icm-deficient Legionella, but not flagellin-deficient Legionella or heat-killed Legionella induced IL-8 expression. L. pneumophila activated an IL-8 promoter through the NF-kappaB and AP-1 binding regions. Wild-type L. pneumophila but not flagellin-deficient Legionella activated NF-kappaB, p38 mitogen-activated protein kinase (MAPK), Jun N-terminal kinase (JNK), and transforming growth factor beta-associated kinase 1 (TAK1). Transfection of dominant negative mutants of IkappaBalpha, IkappaB kinase, NF-kappaB-inducing kinase, TAK1, MyD88, and p38 MAPK inhibited L. pneumophila-induced IL-8 activation. Inhibitors of NF-kappaB, p38 MAPK, and JNK blocked L. pneumophila-induced IL-8 expression. In addition, c-Jun, JunD, cyclic AMP response element binding protein, and activating transcription factor 1, which are substrates of p38 MAPK and JNK, bound to the AP-1 site of the IL-8 promoter.
  
  
  CONCLUSIONS
  Taken together, L. pneumophila induced a flagellin-dependent activation of TAK1, p38 MAPK, and JNK, as well as NF-kappaB and AP-1, which resulted in IL-8 production in human T cells, presumably contributing to the immune response in Legionnaire's disease.
authors.affiliation: Division of Molecular Virology and Oncology, Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa 903-0215, Japan.
authors.forename: Reika
authors.initials: R
authors.lastname: Takamatsu
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Teruya
authors.forename: Eriko
authors.initials: E
authors.lastname: Takeshima
authors.forename: Chie
authors.initials: C
authors.lastname: Ishikawa
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Naofumi
authors.initials: N
authors.lastname: Mukaida
authors.forename: Jian-Dong
authors.initials: JD
authors.lastname: Li
authors.forename: Klaus
authors.initials: K
authors.lastname: Heuner
authors.forename: Futoshi
authors.initials: F
authors.lastname: Higa
authors.forename: Jiro
authors.initials: J
authors.lastname: Fujita
authors.forename: Naoki
authors.initials: N
authors.lastname: Mori
mesh_terms: D005408:Flagellin / Q000276:immunology*; D006801:Humans; D016209:Interleukin-8 / Q000276:immunology* / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D019169:Jurkat Cells; D016952:Legionella pneumophila / Q000276:immunology*; D007877:Legionnaires' Disease / Q000276:immunology; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D000099151:MAP Kinase Kinase Kinase 7
chemical_list: D005408:Flagellin; D016209:Interleukin-8; D048031:JNK Mitogen-Activated Protein Kinases; D020930:MAP Kinase Kinase Kinases; D016328:NF-kappa B; D018808:Transcription Factor AP-1; D048051:p38 Mitogen-Activated Protein Kinases; D000099151:MAP Kinase Kinase Kinase 7