TLR8 agonists stimulate newly recruited monocyte-derived cells into potent APCs that enhance HBsAg immunogenicity.
TLR8 agonists stimulate newly recruited monocyte-derived cells into potent APCs that enhance HBsAg immunogenicity.
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DOI：
10.1016/j.vaccine.2010.06.117
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发表时间：
2010-08-31
期刊：
影响因子：
5.5
通讯作者：
Qu, Chunfeng
中科院分区：
文献类型：
--
作者：
Du, Jun;Wu, Zhiyuan;Ren, Shurong;Wei, Yong;Gao, Meihua;Randolph, Gwendalyn J.;Qu, Chunfeng
我们以前报道过，合成或天然的Toll样受体（TLR）7/8激动剂存在于死细胞内增强细胞相关抗原的提呈在体外和体内。在这里，我们研究了不同的化学合成的TLR 7/8激动剂，瑞喹莫特，Gardiquimod，CL 075和CL 097，对HBsAg免疫原性的免疫效力。这些激动剂刺激炎性单核细胞衍生的细胞成为有效的抗原呈递树突状细胞（DC），其在用HBsAg调节后增强HBsAg特异性T细胞增殖。TLR 8激动剂CL 075和TLR 7/8双重激动剂CL 097显示出比TLR 7激动剂更有效的作用。与明矾佐剂相比，当HBsAg与CL 075混合后肌肉注射到小鼠体内时，更多的单核细胞来源的DC携带抗原进入引流淋巴结和脾脏。在接受HBsAg与CL 075和CL 097混合的小鼠中，特异性Ab，特别是IgG 2a显著增加，并且脾细胞和肝内免疫细胞产生更多的IL-5和IFN-γ。这些结果表明TLR 8激动剂是增强重组HBsAg免疫原性以诱导特异性体液和细胞免疫应答的良好候选物。
We previously reported that synthetic or natural Toll-like receptor (TLR) 7/8 agonists present within dead cells enhanced cell-associated antigen presentation both in vitro and in vivo. Here, we investigated the immunopotency of different chemically synthesized TLR7/8 agonists, Resiquimod, Gardiquimod, CL075, and CL097, on HBsAg immunogenicity. These agonists stimulated inflammatory monocyte-derived cells to become potent antigen-presenting dendritic cells (DCs), which augmented HBsAg specific T cell proliferation after they were conditioned with HBsAg. The TLR8 agonist CL075 and the TLR7/8 dual agonist CL097 showed more potent effects than the TLR7 agonist. Compared with alum adjuvant, when HBsAg mixed with CL075 was injected intramuscularly into mice, more monocyte-derived DCs carried antigens into draining lymph nodes and spleens. Specific Abs, particularly IgG2a, were significantly increased, and more IL-5 and IFN-γ were produced by splenocytes and intrahepatic immunocytes in mice that received HBsAg mixed with CL075 and CL097. These results suggest that TLR8 agonists are good candidates to enhance recombinant HBsAg immunogenicity to induce specific humoral and cellular immune responses.
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