Non-standard viral genome-derived RNA activates TLR3 and type I IFN signaling to induce cDC1-dependent CD8+ T-cell responses during vaccination in mice.
Non-standard viral genome-derived RNA activates TLR3 and type I IFN signaling to induce cDC1-dependent CD8+ T-cell responses during vaccination in mice.
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非标准病毒基因组衍生的 RNA 会激活 TLR3 和 I 型 IFN 信号传导，在小鼠疫苗接种过程中诱导 cDC1 依赖性 CD8 T 细胞反应。
DOI：
10.1016/j.vaccine.2022.10.052
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发表时间：
2022
期刊：
影响因子：
5.5
通讯作者：
López,CarolinaB
中科院分区：
文献类型：
--
作者：
Fisher,DevinG;Gnazzo,Victoria;Holthausen,DavidJ;López,CarolinaB
迫切需要开发疫苗佐剂，其诱导能够保护免受细胞内病原体（包括病毒）的强大免疫应答。以前，我们描述了缺陷病毒基因组衍生的寡核苷酸（DDO）作为新的佐剂，强烈诱导1型免疫应答，包括保护性Th1 CD4+ T细胞和效应CD8+ T细胞在小鼠中。在这里，我们解开了这种1型免疫诱导所需的早期先天反应。在DDO皮下注射后，1型常规树突状细胞（cDC1）以Toll样受体3（TLR3）和I型干扰素（IFN）依赖性方式在引流淋巴结中迅速积累。淋巴结中的cDC 1积累是抗原特异性CD8+ T细胞应答所必需的。值得注意的是，与聚I：C相反，DDO给药导致I型IFN在注射部位表达，但不在引流淋巴结中表达。此外，DDO诱导的炎性细胞因子谱与poly I：C诱导的炎性细胞因子谱不同。因此，DDO代表了在针对细胞内病原体的疫苗接种期间使用的强大的新佐剂。
There is a critical need to develop vaccine adjuvants that induce robust immune responses able to protect against intracellular pathogens, including viruses. Previously, we described defective viral genome-derived oligonucleotides (DDOs) as novel adjuvants that strongly induce type 1 immune responses, including protective Th1 CD4+ T-cells and effector CD8+ T-cells in mice. Here, we unravel the early innate response required for this type 1 immunity induction. Upon DDO subcutaneous injection, type 1 conventional dendritic cells (cDC1s) accumulate rapidly in the draining lymph node in a Toll-like receptor 3 (TLR3)- and type I interferon (IFN)-dependent manner. cDC1 accumulation in the lymph node is required for antigen-specific CD8+ T-cell responses. Notably, in contrast to poly I:C, DDO administration resulted in type I IFN expression at the injection site, but not in the draining lymph node. Additionally, DDOs induced an inflammatory cytokine profile distinct from that induced by poly I:C. Therefore, DDOs represent a powerful new adjuvant to be used during vaccination against intracellular pathogens.