在癌症免疫疗法期间,P型pilus PapG蛋白引发了类似收费受体2介导的免疫激活
Wei Zhang1, Hae-Bin Park2, Dhananjay Yadav3
1Shanghai Public Health Clinical Center and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai 201508, China.
International journal of biological macromolecules
|October 31, 2024
概括
大肠杆菌的PapG蛋白通过与收费类受体2 (TLR2) 相互作用来激活免疫细胞. 这种免疫刺激显示出开发抗癌免疫疗法的潜力.
科学领域:
- 免疫学 免疫学 免疫学
- 微生物学 微生物学
- 癌症研究 癌症研究
背景情况:
- FimH是一种大肠杆菌 (E. coli) 粘附蛋白,已知具有免疫激活作用.
- 另一种大肠杆菌 pili 蛋白 PapG 的免疫活性仍未得到充分研究.
- 了解PapG的免疫调节潜力对于新的治疗策略至关重要.
研究的目的:
- 评估净化复合PapG的免疫刺激作用.
- 为了确定负责PapG介导免疫激活的特定受体.
- 评估PapG作为抗癌免疫疗法的免疫刺激剂的潜力.
主要方法:
- 评估了PapG对骨髓衍生的树突细胞 (BMDCs) 形态,共刺激分子,MHC表达和细胞因子产生的影响.
- 在分析中使用,以预测PapG与小鼠收费类受体2 (TLR2) 的结合亲和力.
- 在TLR2-淘汰赛小鼠和人类外周血液树突细胞 (DCs) 中研究了PapG诱导的免疫反应.
主要成果:
- 帕普基诱导了BMDC形态的显著变化,增加了共刺激分子和MHC I/II表达,并促进了亲炎性细胞因子的产生.
- 在和体内研究证实了PapG与TLR2具有强烈的结合亲和力,在TLR2-淘汰的小鼠中DC激活受损.
- 结合PapG和卵泡胺 (OVA) 增强了OVA特异性T细胞反应和针对OVA表达B16黑色素瘤的抗癌免疫力.
- 帕普G以TLR2依赖的方式激活了人体外围血液的DC和传统的DC2子集,促进了T细胞的增殖和激活.
结论:
- 帕普基作为一种强大的免疫刺激剂,主要通过TLR2参与作用.
- 帕普基显示出增强抗癌免疫反应的显著潜力.
- 帕普基是开发抗癌新型免疫疗法的有前途的候选者.
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