| RRC ID |
19639
|
| 著者 |
Inden K, Kaneko J, Miyazato A, Yamamoto N, Mouri S, Shibuya Y, Nakamura K, Aoyagi T, Hatta M, Kunishima H, Hirakata Y, Itoh Y, Kaku M, Kawakami K.
|
| タイトル |
Toll-like receptor 4-dependent activation of myeloid dendritic cells by leukocidin of Staphylococcus aureus.
|
| ジャーナル |
Microbes Infect
|
| Abstract |
Leukocidin (Luk), an exotoxin of Staphylococcus aureus consisting of LukF and LukS, is a hetero-oligomeric pore-forming cytolytic toxin toward human and rabbit polymorphonuclear leukocytes. However, it is uncertain how Luk affects the host immune response. In the present study, we investigated whether Luk has the ability to stimulate mouse bone marrow-derived myeloid dendritic cells (BM-DCs). LukF activated BM-DCs to generate IL-12p40 mRNA, induce intracellular expression and extracellular secretion of this cytokine and express CD40 on their surface, whereas LukS showed a much lower or marginal ability in the activation of BM-DCs than its counterpart component. Similarly, TNF-alpha was secreted by BM-DCs upon stimulation with these components. Combined addition of these components did not lead to a further increase in IL-12p40 secretion. IL-12p40 production caused by LukF was completely abrogated in BM-DCs from TLR4-deficient mice similarly to the response to lipopolysaccharide (LPS). Polymixin B did not affect the LukF-induced IL-12p40 production, although the same treatment completely inhibited the LPS-induced response. Boiling significantly inhibited the response caused by LukF, but not by LPS. Finally, in a luciferase reporter assay, LukF induced the activation of NF-kappaB in HEK293T cells transfected with TLR4, MD2 and CD14, whereas LukS did not show such activity. These results demonstrate that LukF caused the activation of BM-DCs by triggering a TLR4-dependent signaling pathway and suggests that Luk may affect the host inflammatory response as well as show a cytolytic effect on leukocytes.
|
| 巻・号 |
11(2)
|
| ページ |
245-53
|
| 公開日 |
2009-2-1
|
| DOI |
10.1016/j.micinf.2008.11.013
|
| PII |
S1286-4579(08)00336-5
|
| PMID |
19111627
|
| MeSH |
Animals
Bacterial Proteins / immunology*
CD40 Antigens / biosynthesis
Cell Line
Cells, Cultured
Dendritic Cells / immunology*
Humans
Interleukin-12 Subunit p40 / metabolism
Leukocidins / immunology*
Mice
Mice, Inbred C3H
Mice, Inbred C57BL
Mice, Knockout
NF-kappa B / metabolism
Staphylococcus aureus / immunology*
Toll-Like Receptor 4 / deficiency
Toll-Like Receptor 4 / immunology*
Tumor Necrosis Factor-alpha / metabolism
|
| IF |
2.373
|
| 引用数 |
23
|
|
WOS 分野
|
INFECTIOUS DISEASES
MICROBIOLOGY
IMMUNOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
RAW 264(RCB0535) |
