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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

Toll样受体（TLR）不仅由吞噬细胞表达，也由某些T细胞亚群表达。我们发现，携带Vδ1的上皮γδ T细胞和携带Vα14的肝内NKT细胞表达TLR，在细菌感染时肝损伤的保护和发病中起重要作用。1携带Yδ 1的上皮γδ T细胞中性粒细胞流入感染部位，随后巨噬细胞流入感染部位，在抗大肠杆菌感染的先天免疫中起关键作用。我们发现，Vδ1^<-/->小鼠腹腔接种大肠杆菌后，腹腔巨噬细胞蓄积受损，但中性粒细胞未受损，细菌清除延迟。来自大肠杆菌感染的野生型小鼠的腹膜γδ T细胞在体外响应γδ TCR触发而产生CCL 3/MIP-1 α和CCL 5/RANTES，而这种产生在来自大肠杆菌感染的γδ1 <-/->小鼠的γδ T细胞中不明显。CCL 3/MIP-1a的中和 ...更多信息通过特异性单克隆抗体在体内显著抑制了大肠杆菌感染后腹腔内巨噬细胞的聚集，导致腹腔内细菌生长加剧。这些结果表明，在大肠杆菌感染过程中，Vδ1^+γδ T细胞通过产生CC趋化因子，在天然免疫中桥接嗜中性粒细胞和巨噬细胞之间的间隙，增强巨噬细胞向感染部位的运输。2肝内NKT细胞腹腔接种大肠杆菌后，肝内NK1.1^+ T细胞Fas配体（Fas L）在体内被诱导表达。通过血清GPT水平和组织学检查评估，大肠杆菌感染后的肝损伤在缺乏NK 1.1 ^+ T细胞的Ja 281 ^<-/->小鼠或携带突变Fas L的gld/gld小鼠中显著减轻，表明NK T细胞至少部分以Fas/Fas L依赖的方式参与大肠杆菌诱导的肝损伤。大肠杆菌感染后，Ja 281 ^<-/->小鼠的器官中的细菌数量和血清中的细胞因子水平与Ja 281 ^<+/+>小鼠的器官中的细菌数量和血清中的细胞因子水平没有差异。肝内NK1.1^+ T细胞优先表达TLR 2 mRNA，在体外对合成脂蛋白（TLR 2的配体）的反应是诱导其表面Fas L表达。与大肠杆菌感染相似，脂蛋白和LPS可叠加诱导NK 1.1 ^+ T细胞表达Fas L，导致正常小鼠体内肝损伤，但gld/gld小鼠体内无肝损伤。结论：脂蛋白等细菌成分诱导小鼠NK T细胞表面Fas L表达在大肠杆菌性肝损伤的发病机制中起重要作用。少

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）

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.

Ishimitsu, R.et al.: "NKT cells are dispensable in induction of oral tolerance but indispensable in abrogation of oral tolerance by prostaglandin E"Eur.J.Immunol. 33. 183-193 (2003)

Ishimitsu, R. 等人：“NKT 细胞对于诱导口服耐受是可有可无的，但对于前列腺素 E 消除口服耐受是必不可少的”Eur.J.Immunol。