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Molecular characterization of Legionella pneumophila-induced interleukin-8 expression in T cells

Authors :
Mukaida Naofumi
Matsumoto Kunihiro
Ishikawa Chie
Takeshima Eriko
Teruya Hiromitsu
Takamatsu Reika
Li Jian-Dong
Heuner Klaus
Higa Futoshi
Fujita Jiro
Mori Naoki
Source :
BMC Microbiology, Vol 10, Iss 1, p 1 (2010)
Publication Year :
2010
Publisher :
BMC, 2010.

Abstract

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-κB and AP-1 binding regions. Wild-type L. pneumophila but not flagellin-deficient Legionella activated NF-κB, p38 mitogen-activated protein kinase (MAPK), Jun N-terminal kinase (JNK), and transforming growth factor β-associated kinase 1 (TAK1). Transfection of dominant negative mutants of IκBα, IκB kinase, NF-κB-inducing kinase, TAK1, MyD88, and p38 MAPK inhibited L. pneumophila-induced IL-8 activation. Inhibitors of NF-κB, 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-κB and AP-1, which resulted in IL-8 production in human T cells, presumably contributing to the immune response in Legionnaire's disease.

Subjects

Subjects :
Microbiology
QR1-502

Details

Language :
English
ISSN :
14712180
Volume :
10
Issue :
1
Database :
Directory of Open Access Journals
Journal :
BMC Microbiology
Publication Type :
Academic Journal
Accession number :
edsdoj.0ab2a4e3e26743b4a595ce5ce794f9d1
Document Type :
article
Full Text :
https://doi.org/10.1186/1471-2180-10-1