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Cited by 337

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

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Takamatsu, Reika, Teruya, Hiromitsu, Takeshima, Eriko, Ishikawa, Chie, Matsumoto, Kunihiro, Mukaida, Naofumi, Li, Jian-Dong, Heuner, Klaus, Higa, Futoshi, Fujita, Jiro, Mori, Naoki·2010·BMC Microbiology
DOI 10.1186/1471-2180-10-1
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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.

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Metadata

Authors
Takamatsu, R., Teruya, H., Takeshima, E., Ishikawa, C., Matsumoto, K., Mukaida, N., Li, J.-D., Heuner, K., Higa, F., Fujita, J., & Mori, N.
Venue
BMC Microbiology
Publisher
Springer Science and Business Media LLC
Published
2010-01-05
Volume
10
Issue
1
Pages
1-1
ISSN
1471-2180 (ISSN-L)
DOI
10.1186/1471-2180-10-1
OpenAlex
W2140132276
Cited by
337
References
1
FWCI
7.94
Type
journal article
Language
en
Status
Retracted
Update notices
retraction (2011-06-02)
Open access
gold

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Takamatsu, R., Teruya, H., Takeshima, E., Ishikawa, C., Matsumoto, K., Mukaida, N., Li, J.-D., Heuner, K., Higa, F., Fujita, J., & Mori, N. (2010). Molecular characterization of Legionella pneumophila-induced interleukin-8 expression in T cells. BMC Microbiology. https://doi.org/10.1186/1471-2180-10-1

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