Department of Vaccinology and Applied Microbiology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
Department of Vaccinology and Applied Microbiology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
EBioMedicine. 2017 Aug;22:100-111. doi: 10.1016/j.ebiom.2017.07.016. Epub 2017 Jul 19.
Cyclic di-nucleotides (CDN) are potent stimulators of innate and adaptive immune responses. Cyclic di-AMP (CDA) is a promising adjuvant that generates humoral and cellular immunity. The strong STING-dependent stimulation of type I IFN represents a key feature of CDA. However, recent studies suggested that this is dispensable for adjuvanticity. Here we demonstrate that stimulation of IFN-γ-secreting CD8 cytotoxic T lymphocytes (CTL) is significantly decreased after vaccination in the absence of type I IFN signaling. The biological significance of this CTL response was confirmed by the stimulation of MHC class I-restricted protection against influenza virus challenge. We show here that type I IFN (and not TNF-α) is essential for CDA-mediated cross-presentation by a cathepsin independent, TAP and proteosome dependent cytosolic antigen processing pathway, which promotes effective cross-priming and further CTL induction. Our data clearly demonstrate that type I IFN signaling is critical for CDN-mediated cross-presentation.
环二核苷酸（CDN）是先天和适应性免疫反应的有效刺激物。环二鸟苷酸（CDA）是一种很有前途的佐剂，可产生体液和细胞免疫。STING 依赖性的 I 型干扰素的强烈刺激是 CDA 的一个关键特征。然而，最近的研究表明，这对于佐剂活性不是必需的。在这里，我们证明在缺乏 I 型 IFN 信号的情况下，接种疫苗后 IFN-γ 分泌的 CD8 细胞毒性 T 淋巴细胞（CTL）的刺激显著降低。CTL 反应的生物学意义通过 MHC Ⅰ类限制的流感病毒攻击保护的刺激得到证实。我们在这里表明，I 型 IFN（而非 TNF-α）对于 CDA 介导的通过组织蛋白酶非依赖性、TAP 和蛋白酶体依赖性胞质抗原加工途径的交叉呈递是必需的，该途径促进有效的交叉引发和进一步的 CTL 诱导。我们的数据清楚地表明，I 型 IFN 信号对于 CDN 介导的交叉呈递至关重要。
