Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.
Department of Pathology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.
Clin Exp Allergy. 2015 Sep;45(9):1459-71. doi: 10.1111/cea.12564.
Allergic asthma is a chronic pulmonary disease characterized by a Th2 inflammatory response. The modulation of a Th2 immune response based on immune deviation to a Th1 pattern or induction and migration of regulatory T cells to the lungs constitutes one of the major therapeutic approaches that is being investigated for the treatment of allergic asthma. The potentials of Mycobacterium leprae 65-kD heat-shock protein or Toll-like receptor 9 ligand (CpG oligodeoxynucleotides) as immune modulators for the treatment of airway allergic disease have been studied individually.
Mycobacterial protein combined with CpG was used as immunotherapy for airway allergy.
Using an ovalbumin-induced asthma model, mice were sensitized and challenged, and then treated with mycobacterial heat-shock protein (Hsp65) combined with CpG.
The treatment of mice with established allergy led to the attenuation of eosinophilia, Th2 cytokines and airway hyperresponsiveness. Hsp65 plus CpG treatment also induced an increase in OVA-specific IFN-γ levels and in the frequency of lung inflammatory monocytes. Moreover, we show that the reduction of eosinophilia and the recruitment of inflammatory monocytes to the lungs required early triggering of TLR9, IFN-γ and CCR2 by immunotherapy components.
In addition to immune deviation to a Th1 response in the modulation of Th2 allergic inflammation, our findings also attribute an important role to the innate response mediated by TLR9, associated with the recruitment of CCR2-dependent monocytes.
Our findings show that the Hsp65/CpG treatment is a promising strategy for consideration in translational studies.
过敏性哮喘是一种慢性肺部疾病，其特征为 Th2 炎症反应。基于向 Th1 模式的免疫偏离或诱导和调节性 T 细胞向肺部迁移来调节 Th2 免疫反应，构成了正在研究的治疗过敏性哮喘的主要治疗方法之一。麻风分枝杆菌 65kDa 热休克蛋白或 Toll 样受体 9 配体（CpG 寡脱氧核苷酸）作为免疫调节剂用于治疗气道过敏性疾病的潜力已分别进行了研究。
将分枝杆菌蛋白与 CpG 联合用于气道过敏的免疫治疗。
使用卵清蛋白诱导的哮喘模型，对致敏和激发的小鼠进行分枝杆菌热休克蛋白（Hsp65）联合 CpG 治疗。
对已建立过敏的小鼠进行治疗可减轻嗜酸性粒细胞增多、Th2 细胞因子和气道高反应性。Hsp65 加 CpG 治疗还诱导了 OVA 特异性 IFN-γ 水平和肺部炎症性单核细胞频率的增加。此外，我们表明嗜酸性粒细胞减少和炎症性单核细胞向肺部募集需要 TLR9、IFN-γ 和 CCR2 免疫治疗成分的早期触发。
除了调节 Th2 过敏炎症的向 Th1 反应的免疫偏离外，我们的发现还将 TLR9 介导的先天反应以及与 CCR2 依赖性单核细胞募集相关的重要作用归因于该反应。
我们的研究结果表明，Hsp65/CpG 治疗是一种有前途的转化研究策略。
