Related Experiment Video
Updated: Jun 17, 2026
Legionella pneumophila Outer Membrane Vesicles: Isolation and Analysis of Their Pro-inflammatory Potential on Macrophages
Published on: February 22, 2017
Molecular characterization of Legionella pneumophila-induced interleukin-8 expression in T cells
Reika Takamatsu1, Hiromitsu Teruya, Eriko Takeshima
1Division of Molecular Virology and Oncology, Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa 903-0215, Japan.
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.
Insights
Legionella pneumophila infects human T cells, triggering interleukin-8 (IL-8) production via flagellin-dependent pathways. This interaction, involving NF-kappaB and AP-1 activation, contributes to the immune response in Legionnaire's disease.
Area of Science:
- Immunology
- Microbiology
- Cell Biology
Background:
- Legionella pneumophila causes Legionnaire's disease by infecting macrophages and lung epithelial cells.
- The interaction of L. pneumophila with T cells and its role in immune response are poorly understood.
- This study investigates L. pneumophila's ability to infect T cells and induce interleukin-8 (IL-8) production.
Purpose of the Study:
- To determine if L. pneumophila can infect human T cells.
- To investigate L. pneumophila's capacity to stimulate IL-8 production in T cells.
- To elucidate the molecular mechanisms underlying L. pneumophila-induced immune responses in T cells.
Main Methods:
- Assessed bacterial replication in T cells using wild-type and mutant L. pneumophila strains (flagellin-deficient, Dot/Icm-deficient).
- Measured IL-8 expression and promoter activity in response to L. pneumophila infection.
- Utilized reporter assays, dominant-negative mutants, and pathway inhibitors (NF-kappaB, p38 MAPK, JNK) to dissect signaling pathways.
Main Results:
- Wild-type and flagellin-deficient L. pneumophila replicated in T cells, while Dot/Icm-deficient strains did not.
- Wild-type and Dot/Icm-deficient L. pneumophila induced IL-8 expression, dependent on flagellin and Dot/Icm.
- L. pneumophila activated the IL-8 promoter via NF-kappaB and AP-1, involving TAK1, p38 MAPK, and JNK signaling pathways.
Conclusions:
- L. pneumophila induces IL-8 production in human T cells through a flagellin-dependent activation of TAK1, p38 MAPK, JNK, NF-kappaB, and AP-1.
- This interaction suggests a role for T cells in the immune response to Legionnaire's disease.
- The findings highlight novel mechanisms of bacterial interaction with the adaptive immune system.
