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: Reika Takamatsu, Hiromitsu Teruya, Eriko Takeshima, Chie Ishikawa, Kunihiro Matsumoto, Naofumi Mukaida, Jian-Dong Li, Klaus Heuner, Futoshi Higa, Jiro Fujita, Naoki Mori
• Journal: BMC microbiology (BMC Microbiol) Vol. 10 Pg. 1 (Jan 05 2010) ISSN: 1471-2180 [Electronic] England
• PMID: 20051107 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Retracted Publication)

Chemical References

• Interleukin-8
• NF-kappa B
• Transcription Factor AP-1
• Flagellin
• JNK Mitogen-Activated Protein Kinases
• p38 Mitogen-Activated Protein Kinases
• MAP Kinase Kinase Kinases
• MAP kinase kinase kinase 7

Topics

• Flagellin (immunology)
• Humans
• Interleukin-8 (immunology, metabolism)
• JNK Mitogen-Activated Protein Kinases (metabolism)
• Jurkat Cells
• Legionella pneumophila (immunology)
• Legionnaires' Disease (immunology)
• MAP Kinase Kinase Kinases (metabolism)
• NF-kappa B (metabolism)
• Phosphorylation
• Promoter Regions, Genetic
• T-Lymphocytes (immunology, metabolism)
• Transcription Factor AP-1 (metabolism)
• p38 Mitogen-Activated Protein Kinases (metabolism)