Immunity:接触细菌DNA能预防和治疗过敏性哮喘

2017-03-23 Leo.C MedSci原创

接触细菌DNA能过预防和治疗过敏性哮喘

进十几年来过敏性哮喘的发生率持续上升,尤其是在发达国家地区。传统的卫生假设理论(hygiene hypothesis)推测,上升的哮喘发病率是因为人们减少了接触细菌及各种微生物,以及城市化所引起的。为了对抗致病细菌对人体的感染,机体发展出多种系统来识别细菌的各个组成部分。其中细菌的DNA能够被免疫细胞的toll-like receptor 9, TLR9所识别。细菌的DNA普遍存在于空气土壤和灰尘中。在疫苗制备中,合成的细菌DNA片段(CpG)被用来作为辅助剂来增强机体对疫苗的免疫反应。然而,多项报导显示细菌DNA片段(CpG)能够预防或者抑制哮喘的发生。

在最近的一期Immunity杂志中,Catherine Sabatel及其同事证明了细菌DNA片段(CpG)对于过敏性哮喘的防治作用。

研究团队发现,通过鼻部吸入细菌DNA片段(CpG)能够增加肺部的局部巨噬细胞(macrophages)的数量。肺部的巨噬细胞通常和肺部的树突状细胞(dendritic cells)的位置相近。树突状细胞的功能是识别所暴露的抗原然后呈现给在组织和淋巴的T细胞引起免疫反应。过度的免疫反应就会形成过敏性哮喘。接触细菌DNA片段(CpG)所增加的巨噬细胞能够阻断树突状细胞将抗原呈现给T细胞,并且开始分泌大量的细胞激素IL10。细胞激素IL10具有广泛的抑制发炎的作用,更重要的是IL10的分泌能过调节原来促炎的T细胞分化为抑制炎症的调节性T细胞(Treg),从而进一步抑制过敏性哮喘。在缺失IL10的老鼠上,这种保护效果就消失了。

另外,研究组进一步发现这些在肺部的巨噬细胞是从肺部和脾脏的游弋的单核细胞接受了细菌DNA片段(CpG)的刺激以后分化和迁移而来。如果在实验鼠上敲除了细菌DNA的识别受体TLR9,则在肺部的巨噬细胞的数量大量减少。

此项研究支持了少量接触细菌微生物能够预防治疗过免疫性疾病,例如过敏性哮喘这一假设,并未哮喘的治疗和预防提供了新的思路。

原始出处:
Catherine Sabatel, Coraline Radermecker, Laurence Fievez et al. Exposure to Bacterial CpG DNA Protects from Airway Allergic Inflammation by Expanding Regulatory Lung Interstitial Macrophages. Immunity 457–473 March 21, 2017 2017 http://dx.doi.org/10.1016/j.immuni.2017.02.016

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    2017-03-24 1de33cf7m09(暂无匿称)

    很好。

    0

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