Microbe recognition and effect on TLR response by C-type lection expressing in immune cells.

免疫细胞中表达的 C 型分泌物对微生物的识别及其对 TLR 反应的影响。

• 批准号: 17590342
• 负责人: TAKAHARA Kazuhiko
• 金额: $ 2.3万
• 依托单位: Kyoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17590342/
• 关键词: lectin; TLR4; TLR2; macrophage; Gram-negative bacteria; cytokine; Candida albicans; lipopolysaccharide; RAW264.7; Zymosan; 樹状細胞; TLR; 酵母; DC-SIGN

C-type lectins in immune system play a roll in pattern recognition receptor (PRR) against surface polysaccharide on microbes. We are investigating new aspects of lectins in cooperation with another PRR, toll-like receptor (TLR). In this study, we focus in the cooperation with SIGNR1 and TLR4 and revealed points as follows:1)SIGNRl physically binds TLR2.2)SIGNRl enhances TLR2/MD-2 oligomerization after stimulation with Gram-negative bacteria.3)SIGNR1 recognizes non-reductive end of LPS core polysaccharide.4)SINGR1 is a major receptor against model polysaccharide antigen dextran on resident peritoneal macrophages (rpMφ).5)rpMφ enhances TN F-a production against S. typhimurium via SIGNR1.6)Transfection of SIGNR1 improves TNF-a production form RAW264.7.7)SIGNRl also binds TLR2.8)RAW264.7 expressing SIGNR1 acquires Candicidal activity.9)Soluble SIGNR1 binds hyphae form of C. albicans.10)During infection to cells, SIGNR1 localizes at the invading sites of C. albicans.These results suggest that SIGNR1 cooperates with TLR4 and TLR2 in response to Gram-negative bacteria and C. albicans, respectively, and plays roles in innate and acquired immunity. In addition, we generated new monoclonal antibody against another SIGNR family, SIGNR3. Using this antibody, we are investigating its expression pattern in vivo.

免疫系统中的 C 型凝集素在对抗微生物表面多糖的模式识别受体 (PRR) 中发挥作用。我们正在与另一种 PRR、Toll 样受体 (TLR) 合作研究凝集素的新方面。在本研究中，我们重点关注SIGNR1和TLR4的合作，揭示了以下几点：1）SIGNR1物理结合TLR2。2）SIGNR1在革兰氏阴性菌刺激后增强TLR2/MD-2寡聚化。3）SIGNR1识别LPS核心多糖的非还原端。4）SINGR1是针对模型多糖抗原的主要受体 腹膜巨噬细胞上的葡聚糖 (rpMφ).5)rpMφ 通过 SIGNR1.6) 增强针对鼠伤寒沙门氏菌的 TNF-a 产生。 6) SIGNR1 转染提高 RAW264.7.7) SIGNR1 还结合 TLR2.8) 表达 SIGNR1 的 RAW264.7 获得念珠菌活性。 9) 可溶性 SIGNR1 结合 10)在细胞感染过程中，SIGNR1定位于白色念珠菌的入侵位点。这些结果表明，SIGNR1与TLR4和TLR2协同作用，分别对革兰氏阴性菌和白色念珠菌作出反应，并在先天性和获得性免疫中发挥作用。此外，我们还针对另一个 SIGNR 家族 SIGNR3 生成了新的单克隆抗体。使用这种抗体，我们正在研究其体内表达模式。

项目成果

Probing Langerhans cell function by their inducible ablation in mice.

通过小鼠中朗格汉斯细胞的诱导消融来探索朗格汉斯细胞的功能。

• 发表时间: 2005
• 期刊: J. Cell. Biol. 169

Association of SIGNR1 with TLR4/MD-2 enhances signal transduction by recognition of LPS in Gram-negative

SIGNR1 与 TLR4/MD-2 的结合通过识别革兰氏阴性菌中的 LPS 来增强信号转导

• 发表时间: 2005
• 期刊: Int.Immunol 17
• 作者: Nagaoka;K.
• 通讯作者: K.

C-type lectins on dendritic cells and macrophages.

树突状细胞和巨噬细胞上的 C 型凝集素。

• 发表时间: 2006
• 期刊: Proceeding of International Symposium on Low-dose Radiation Exposures and Bio-Defence System. (印刷中)
• 作者: Takahara;K.
• 通讯作者: K.

Association of SIGNR1 with TLR4-MD-2 enhances signal transduction by recognition of LPS in gram-negative bacteria.

• DOI: 10.1093/intimm/dxh264
• 发表时间: 2005-07
• 期刊: International immunology
• 影响因子: 4.4
• 作者: K. Nagaoka;K. Takahara;Kay Tanaka;H. Yoshida;R. Steinman;S. Saitoh;Sachiko Akashi-Takamura;K. Miyake;Young‐Sun Kang;Chae Gyu Park;K. Inaba