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分支杆菌 avium subsp. paratuberculosis 纤连蛋白附着蛋白，一种 toll 样受体 4 激动剂，增强基于树突状细胞的癌症疫苗效力。

The Mycobacterium avium subsp. paratuberculosis fibronectin attachment protein, a toll-like receptor 4 agonist, enhances dendritic cell-based cancer vaccine potency.

机构信息

Department of Microbiology and Immunology, School of Medicine, Pusan National University, Yangsan 626-870, Korea Research Institute of Convergence of Biomedical Science and Technology, Pusan National University, Yangsan 626-770, Korea.

出版信息

Exp Mol Med. 2012 May 31;44(5):340-9. doi: 10.3858/emm.2012.44.5.038.

DOI:10.3858/emm.2012.44.5.038
PMID:22322306
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3366327/
Abstract

In this study, we showed the direct interaction between Mycobacterium avium subsp. paratuberculosis fibronectin attachment protein (FAP) and toll-like receptor4 (TLR4) via co-localization and binding by using confocal microscopy and co-immunoprecipitation assays. FAP triggered the expression of pro- and antiinflammatory cytokines in a TLR4-dependent manner. In addition, FAP-induced cytokine expression in bone marrow-derived dendritic cells (BMDCs) was modulated in part by glycogen synthase kinase-3 (GSK-3). FAP-induced expression of CD80, CD86, major histocompatibility complex (MHC) class I, and MHC class II in TLR4(+/+) BMDCs was not observed in TLR4(-/-) BMDCs. Furthermore, FAP induced DC-mediated CD8(+) T cell proliferation and cytotoxic T lymphocyte (CTL) activity, and suppressed tumor growth with DC-based tumor vaccination in EG7 thymoma murine model. Taken together, these results indicate that the TLR4 agonist, FAP, a potential immunoadjuvant for DC-based cancer vaccination, improves the DC-based immune response via the TLR4 signaling pathway.

摘要

在这项研究中，我们通过共聚焦显微镜和共免疫沉淀实验显示了分枝杆菌 avium subsp. 副结核分枝杆菌纤连蛋白附着蛋白 (FAP) 与 toll 样受体 4 (TLR4) 之间的直接相互作用。FAP 通过 TLR4 依赖性方式触发前炎症和抗炎细胞因子的表达。此外，FAP 在骨髓来源的树突状细胞 (BMDC) 中诱导的细胞因子表达部分受到糖原合酶激酶-3 (GSK-3) 的调节。在 TLR4(-/-) BMDC 中未观察到 TLR4(+/+) BMDC 中 FAP 诱导的 CD80、CD86、主要组织相容性复合体 (MHC) 类 I 和 MHC 类 II 的表达。此外，FAP 诱导了 DC 介导的 CD8(+) T 细胞增殖和细胞毒性 T 淋巴细胞 (CTL) 活性，并通过基于 DC 的肿瘤疫苗接种在 EG7 胸腺瘤小鼠模型中抑制肿瘤生长。总之，这些结果表明，TLR4 激动剂 FAP 作为一种潜在的 DC 基癌症疫苗佐剂，通过 TLR4 信号通路改善了基于 DC 的免疫反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9aa4/3366327/27ea4ed9831e/emm-44-340-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9aa4/3366327/b559e2486db2/emm-44-340-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9aa4/3366327/1d39d9fad9c4/emm-44-340-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9aa4/3366327/6e3fbd280a96/emm-44-340-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9aa4/3366327/5ed43b40d116/emm-44-340-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9aa4/3366327/27ea4ed9831e/emm-44-340-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9aa4/3366327/b559e2486db2/emm-44-340-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9aa4/3366327/1d39d9fad9c4/emm-44-340-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9aa4/3366327/6e3fbd280a96/emm-44-340-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9aa4/3366327/5ed43b40d116/emm-44-340-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9aa4/3366327/27ea4ed9831e/emm-44-340-g005.jpg

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