Effect of cigarette smoke on mucosal vaccine response with activation of plasmacytoid dendritic cells: The outcomes of in vivo and in vitro experiments
Effect of cigarette smoke on mucosal vaccine response with activation of plasmacytoid dendritic cells: The outcomes of in vivo and in vitro experiments
复制标题
DOI：
10.1016/j.vaccine.2023.01.019
复制
发表时间：
2023-02-14
期刊：
影响因子：
5.5
通讯作者：
Iho，Sumiko
中科院分区：
文献类型：
--
作者：
Suzuki，Fumiko;Maeyama，Jun-ichi;Iho，Sumiko
粘膜疫苗提供了几个优于透皮疫苗的优点，包括获得全身和粘膜免疫的能力。吸烟是一个巨大的公共卫生威胁和各种疾病的主要风险因素，加剧或延长呼吸道症状和状况。然而，其对粘膜疫苗效力的影响仍在部分探索中。因此，本研究通过评估Th 1免疫（感染防御中的重要反应）的诱导来研究吸烟对粘膜疫苗反应性的影响。制备了卷烟烟气冷凝物作为主流烟气的替代物。我们鼻内给药白喉类毒素作为抗原和天然CpG寡核苷酸G9.1，其以浆细胞样树突状细胞（pDC）依赖的方式增强Th 1型抗体（Ab）应答，作为佐剂给小鼠以评估香烟烟雾冷凝物对Ab应答的影响。使用人外周血单个核细胞及其富含pDC的部分与或不与G9.1一起培养来评价其作用机制。在小鼠中，香烟烟雾冷凝物倾向于降低白喉类毒素特异性抗体反应，其中Th 1型IgG 2抗体反应的降低程度高于Th 2型IgG 1抗体反应。在人外周血单个核细胞中，香烟烟雾冷凝物显著降低了G9.1对IFN-α产生的诱导作用。此外，G9.1诱导的pDC中CD 83表达和DC中CD 80表达的增加通过用香烟烟雾冷凝物处理而被抑制。其中的机制，建议Toll样受体9 mRNA的表达减少，IFN调节因子7的mRNA表达减少，其启动子区域的CpG甲基化增加。Tbet 3和GATA 3表达的分析表明，香烟烟雾冷凝物在稳态下表现出Th 1导向的免疫刺激活性，但在G9.1刺激下变得更多的Th 2导向。总之，吸烟可通过降低pDC活化，从而降低Th 1-显性免疫来降低粘膜疫苗应答。
Mucosal vaccines offer several advantages over transdermal vaccines, including the ability to acquire systemic and mucosal immunities. Smoking is a huge public health threat and major risk factor for various diseases that exacerbate or prolong respiratory symptoms and conditions. However, its impact on the efficacy of mucosal vaccines remains partially explored. Thus, this study investigates the effects of smoking on mucosal vaccine reactivity by assessing the induction of Th1 immunity, a vital response in infection defense. Cigarette smoke condensate was prepared as a substitute for mainstream smoke. We intranasally administered diphtheria toxoid as an antigen and natural CpG oligonucleotide G9.1, which enhances the Th1-type antibody (Ab) response in a plasmacytoid dendritic cells (pDCs) dependent manner, as an adjuvant to mice to assess the effect of cigarette smoke condensate on Ab responses. The mechanism of its effect was evaluated using human peripheral blood mononuclear cells and their pDC-rich fraction cultured with or without G9.1. In mice, cigarette smoke condensate tended to decrease diphtheria toxoid-specific Ab response, with a higher reduction in Th1-type IgG2 Ab response than in Th2-type IgG1 Ab response. In human peripheral blood mononuclear cells, cigarette smoke condensate significantly reduced the induction of IFN-α production by G9.1. Moreover, G9.1-induced increases in the CD83 expression in pDCs and the CD80 expression in DCs were suppressed via treatment with cigarette smoke condensate. Among the mechanisms suggested were decreased expression of toll-like receptor 9 mRNA, decreased expression of mRNA for IFN regulatory factor 7, and increased CpG methylation of its promoter region. The analysis ofTbetandGATA3expressions revealed that cigarette smoke condensate exhibits Th1-directed immunostimulatory activity at a steady state but becomes more Th2-directed under G9.1 stimulation. In conclusion, smoking could reduce mucosal vaccine responses by decreasing pDC activation and, consequently, Th1-dominant immunity.