Department of Immunology, Hebei Medical University, Shijiazhuang, 050017, China.
Department of Biology, Cangzhou Medical College, Cangzhou, 061001, China.
Curr Med Sci. 2019 Jun;39(3):363-370. doi: 10.1007/s11596-019-2044-0. Epub 2019 Jun 17.
Respiratory syncytial virus (RSV) infection is the primary cause of respiratory disease in infants. The formalin-inactivated RSV (FI-RSV) vaccine resulted in an enhanced respiratory disease (ERD) in infants upon natural RSV infection, which is a major obstacle for development of safe and efficacious vaccines. Excessive and uncontrolled Th immune responses could be involved in the ERD. Agonists of TLRs are used as adjuvants to guide the type of immune response induced by vaccines. We evaluated the impact of lipopolysaccharide (LPS), the agonist of TLR4, on ERD as the adjuvant of FI-RSV. The results showed that LPS remarkably inhibited FI-RSV-enhanced lung inflammation, mucus production, airway inflammatory cell infiltration, and inflammatory cytokines following RSV challenge. Interestingly, LPS inhibited both Th2 and Th17 type cytokines in lungs of FI-RSV-immunized mice following RSV challenge, without an increase in the Th1 type cytokines, suggesting a controlled immune response. In contrast, Pam3Cys and Poly(I:C), the agonist of TLR1/2 or TLR3, partly inhibited FI-RSV-enhanced lung inflammation. Pam3Cys inhibited Th17 type cytokine IL-17, but promoted both Th1 and Th2 type cytokines. Poly(I:C) inhibited Th2 and Th17 type cytokines, but promoted Th1 type cytokines. In addition, LPS promoted IgG and IgG2a antibody production, which might provide protection from RSV challenge. These results suggest that LPS inhibits ERD without impairment in antibody production and protection, and the mechanism appears to be related with regulation of Th responses induced by FI-RSV.
呼吸道合胞病毒（RSV）感染是婴儿呼吸道疾病的主要原因。福尔马林灭活的 RSV（FI-RSV）疫苗在自然 RSV 感染后导致婴儿发生增强型呼吸道疾病（ERD），这是安全有效的疫苗开发的主要障碍。过度和不受控制的 Th 免疫反应可能与 ERD 有关。TLR 激动剂被用作佐剂来指导疫苗引起的免疫反应类型。我们评估了脂多糖（LPS），TLR4 的激动剂，作为 FI-RSV 的佐剂对 ERD 的影响。结果表明，LPS 可显著抑制 FI-RSV 增强的肺部炎症、粘液产生、气道炎症细胞浸润和 RSV 攻击后的炎症细胞因子。有趣的是，LPS 抑制了 RSV 攻击后 FI-RSV 免疫小鼠肺部的 Th2 和 Th17 型细胞因子，而 Th1 型细胞因子没有增加，表明免疫反应得到了控制。相比之下，Pam3Cys 和 Poly(I:C)，TLR1/2 或 TLR3 的激动剂，部分抑制了 FI-RSV 增强的肺部炎症。Pam3Cys 抑制了 Th17 型细胞因子 IL-17，但促进了 Th1 和 Th2 型细胞因子。Poly(I:C) 抑制了 Th2 和 Th17 型细胞因子，但促进了 Th1 型细胞因子。此外，LPS 促进了 IgG 和 IgG2a 抗体的产生，这可能为 RSV 攻击提供保护。这些结果表明，LPS 抑制 ERD 而不损害抗体产生和保护作用，其机制似乎与 FI-RSV 诱导的 Th 反应的调节有关。
