The roles of primitive T cells bearing Toll-like receptor in microbial infection.

携带Toll样受体的原始T细胞在微生物感染中的作用。

基本信息

批准号：
14370091
负责人：
YOSHIKAI Yasunobu
金额：
$ 9.54万
依托单位：
KYUSHU UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14370091/
关键词：
Toll-like receptor γδ T cell NKT cell E.coli Chemokine host defense Fas-L Liver injury 好中球マクロファージ Vδ1 ノックアウトマウスサルモネラ感染肝臓傷害 JNK 胆管結紮 JIP3 TLR-2 ノックアウトマウス

项目摘要

Toll-like receptors (TLRs) for bacterial constitutes, are expressed not only by phagocytes but also by some subsets of T cells. We have found that epithelial γδ T cells bearing Vδ1 and intrahepatic NKT cells bearing Vα14 expressed TLRs and play an important role in protection and pathogenesis of liver injury during bacterial infection. as follows.1 Epithelial γδ T cells bearing Yδ1An influx of neutrophils followed a short time later by an influx of macrophages to the infected site plays a key role in innate immunity against Eschelichia coli infection. We found that Vδ1^<-/-> mice exhibited impaired accumulation of peritoneal macrophages but not neutrophils and delayed bacterial clearance after intraperitoneal inoculation with E.coli. Peritoneal γδ T cells from E.coli-infected wild-type mice produced CCL3/MIP-la and CCL5/RANTES in response to γδ TCR triggering in vitro, while such production was not evident in γδ T cells from E.coli-infected γδ1^<-/-> mice. Neutralization of CCL3/MIP-la … More by a specific monoclonal antibody in vivo significantly inhibited the accumulation of macrophages in the peritoneal cavity after E.coli infection, resulting in exacerbated bacterial growth in the peritoneal cavity. These results suggest that Vδ1^+γδ T cells bridge a gap between neutrophis and macrophages in innate immunity during E.coli infection mediated by production of CC chemokines, enhancing macrophage trafficking to the site of infection.2 Intrahepatic NKT cellsFas ligand (Fas L) expression was induced on intraheaptic NK1.1^+ T cells in vivo after an intraperitoneal inoculation of Escherichia coli. Liver injury after E.coli infection, as assessed by serum GPT level and histological examination, was significantly reduced in Ja281^<-/-> mice lacking NK1.1^+ T cells or in gld/gld mice bearing mutated Fas L, indicating that NK T cells at least partly contribute to E.coli-induced liver injury in a Fas/Fas L-dependent manner. Bacterial numbers in organs and cytokine levels in serum of Ja281^<-/-> mice did not differ from those of Ja281^<+/+> mice following E.coli infection. Intrahepatic NK1.1^+ T cells, which preferentially expressed TLR2mRNA, responded in vitro to synthetic lipoprotein, a ligand for TLR2, by inducing Fas L expression on their surface. In a manner analogous to E.coli infection, lipoprotein and LPS could additively induce Fas L expression on NK1.1^+ T cells, leading to liver injury in vivo in normal mice but not in gld/gld mice. In conclusion, it is suggested that induction of Fas L on NK T cells in response to bacterial components such as lipoproteins plays an important role in pathogenesis of E.coli-induced liver injury in mice. Less

吞噬细胞的收费表（TLR）（TLR）并非由吞噬细胞表达，而是发现带有vΔ1和带有Vα14内ep eprric nkt细胞的thelialγδT细胞表达了TLR，并在肝损伤的保护和病原体中起重要作用在细菌感染中，不久之后，巨噬细胞向感染部位涌入，在对埃斯利希亚大肠杆菌的先天免疫力中起着关键作用。清除Antr antry用大肠杆菌接种。来自E.COLI感染的γδ1^ - / - CCL3/MIP-LA的中和…更多地是由特异性的单克隆抗体在体内的特定单克隆抗体在腹膜腔中显着抑制。 +γδT细胞在由CC趋化因子介导的大肠杆菌中桥接巨噬细胞巨噬细胞和先天免疫的年龄，增强了巨噬细胞运输到感染部位的巨噬细胞。2Elsfas配体（FAS L）表达在原内的NK1.1.1.1.1.1^+ T -Cells上诱导在缺乏NK1.1.1.1.1.1.1 ^+ T细胞中，通过血清GPT水平和组织学检查评估的大肠杆菌感染后的肝损伤，大肠杆菌感染后的肝损伤显着降低携带fas l的小鼠表明NK T细胞至少有助于fas/fas l依赖性的e.lain肝损伤。 ^<+/+>小鼠e.coli感染类似于E.coli，脂蛋白和LPS可以在NK1.1^+ T细胞上添加fas l表达，在正常小鼠中的肝脏ury ury，但在GLD/GLD小鼠中却不能。 NK T细胞响应细菌诱导的小鼠肝损伤

项目成果

期刊论文数量（190）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Yajima, T.et al.: "Overexpression of IL-15 increases susceptibility to lethal endotoxic shock in mice primed with Mycobacterium bovis BCG"Infect.Immun.. In press. (2004)

Yajima, T. 等人：“IL-15 的过度表达增加了用牛分枝杆菌 BCG 引发的小鼠对致死性内毒素休克的敏感性”Infect.Immun.. 正在出版。

DOI：
发表时间：
期刊：
影响因子：
0
作者：
通讯作者：

Oral adminstration of bovine colostrum stimultes intestinal intraepithelial lymphocytes to polarize Th1-type in mice.

口服牛初乳可刺激小鼠肠上皮内淋巴细胞极化 Th1 型。

DOI：
发表时间：
2005
期刊：
Int.Immunopharm. 5
影响因子：
0
作者：
Yoshioka;Y.;Kudo;S.;Saito K.;Nishimura H.;Yajima;T.;Kishihara K.;Kuroiwa;S.;Suzuki;Y.;Suzuki;T.;Yoshikai Y.
通讯作者：
Yoshikai Y.

Matsuguchi, T.et al.: "Lipoteichoic acids from Lactobacillus strains elicit strong tumor necrosis factor alpha-Inducing activities in macrophages through Toll-like receptor 2"Clin.Diagn.Lab.Immunol.. 10. 259-266 (2003)

Matsuguchi, T.等人：“来自乳杆菌菌株的脂磷壁酸通过 Toll 样受体 2 在巨噬细胞中引发强肿瘤坏死因子 α 诱导活性”Clin.Diagn.Lab.Immunol.. 10. 259-266 (2003)