Combination of TLR8 and TLR4 agonists reduces the degrading effects of nicotine on DC-NK mediated effector T cell generation.
Combination of TLR8 and TLR4 agonists reduces the degrading effects of nicotine on DC-NK mediated effector T cell generation.
复制标题
TLR8 和 TLR4 激动剂的组合可减少尼古丁对 DC-NK 介导的效应 T 细胞生成的降解作用。
DOI：
10.1016/j.intimp.2018.05.012
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发表时间：
2018
影响因子：
5.6
通讯作者：
Guinet,Elisabeth
中科院分区：
文献类型：
--
作者：
Nouri-Shirazi,Mahyar;Tamjidi,Saba;Nourishirazi,Erika;Guinet,Elisabeth
对疫苗接种的免疫应答的程度是确定疾病保护的关键因素。众所周知，香烟烟雾会抑制免疫系统，增加疫苗可预防疾病的风险。我们报道了尼古丁，香烟烟雾的免疫抑制成分，破坏DC的分化和功能特性，这是启动对疫苗的免疫应答的关键。我们还报道了TLR激动剂协同作用并促进DC成熟，DC-NK串扰并最终将幼稚T细胞极化为效应Th 1和Tc 1细胞。我们研究了TLR激动剂的联合应用是否能减弱尼古丁对DC-NK介导的效应性T细胞生成的抑制作用，发现无论是单独使用还是联合使用TLR激动剂，都不能完全减弱尼古丁对DC的不利影响。然而，TLR 3，TLR 4和TLR 8激动剂作为最有效的佐剂，以增加尼古丁暴露的DC（nicDC）的抗原呈递，共刺激分子的表达水平和细胞因子的产生。当组合时，TLR 3 + 8和TLR 4 + 8协同优化共培养期间尼古丁暴露的NK（nicNK）的nicDC成熟和IFN-γ分泌。有趣的是，与DC-NK-T相反，用TLR 3 + 8或TLR 4 + 8激动剂处理的nicDC-nicNK-T的共培养物产生了相似频率的效应记忆Th 1和Tc 1细胞。然而，当与铝盐处理的共培养物相比时，来自TLR 4 + 8然后是TLR 3 + 8处理的nicDC-nicNK-T共培养物的效应细胞产生显著更多的IFN-γ。我们的数据表明，在疫苗制剂中加入适当的TLR激动剂可能会增加吸烟者对疫苗接种的免疫应答。
The magnitude of immune responses to vaccination is a critical factor in determining protection from disease. It is known that cigarette smoke dampens the immune system and increases the risk of vaccine-preventable diseases. We reported that nicotine, the immunosuppressive component of cigarette smoke, disrupts the differentiation and functional properties of DC, which are pivotal in the initiation of immune response to vaccines. We also reported that TLR agonists act in synergy and boost DC maturation, DC-NK crosstalk and ultimately naïve T cell polarization into effector Th1 and Tc1 cells. Here, we investigated whether the combination of TLR agonists could diminish the degrading effects of nicotine on DC-NK mediated effector T cell generation.We found that none of TLR agonists, single or combined, were able to diminish completely the adverse effects of nicotine on DC. However, TLR3, TLR4, and TLR8 agonists acted as the most effective adjuvants to increase the expression levels of antigen-presenting, costimulatory molecules and production of cytokines by nicotine-exposed DC (nicDC). When combined, TLR3 + 8 and TLR4 + 8 synergistically optimized nicDC maturation and IFN-γ secretion from nicotine-exposed NK (nicNK) during co-cultures. Interestingly, in contrast to DC-NK-T, co-cultures of nicDC-nicNK-T treated with TLR3 + 8 or TLR4 + 8 agonists produced a similar frequency of effector memory Th1 and Tc1 cells. However, the effector cells from TLR4 + 8 followed by TLR3 + 8 treated nicDC-nicNK-T co-cultures produced significantly more IFN-γ when compared with aluminum salt treated co-culture. Our data suggest that addition of appropriate TLR agonists to vaccine formulation could potentially augment the immune response to vaccination in smokers.