Intranasal Administration of Recombinant Mycobacterium smegmatis Inducing IL-17A Autoantibody Attenuates Airway Inflammation in a Murine Model of Allergic Asthma.
Intranasal Administration of Recombinant Mycobacterium smegmatis Inducing IL-17A Autoantibody Attenuates Airway Inflammation in a Murine Model of Allergic Asthma.
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DOI：
10.1371/journal.pone.0151581
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Zhang J
中科院分区：
文献类型：
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作者：
Xu W;Chen L;Guo S;Wu L;Zhang J
哮喘是一种慢性炎症性疾病，前期研究表明IL-17A有助于哮喘的发生，且IL-17A水平与疾病严重程度呈正相关。在此，我们构建了表达融合蛋白Ag85A-IL-17A（rMS-Ag85a-IL-17a）的重组耻垢分枝杆菌，并评估其是否可以减轻过敏性气道炎症，并进一步研究其潜在机制。在这项工作中，用卵清蛋白建立了小鼠哮喘模型，并给小鼠鼻内接种了rMS-Ag85a-IL-17a疫苗。检测血清中IL-17A自身抗体，观察气道炎症细胞浸润、局部细胞因子和趋化因子的产生以及肺组织的组织病理学变化。我们发现给予rMS-Ag85a-IL-17a可诱导血清中产生IL-17A自身抗体。接种rMS-Ag85a-IL-17a可显着减少肺组织炎症细胞的浸润和粘液的分泌，并显着减少BALF中的细胞总数、嗜酸性粒细胞和中性粒细胞数量。 rMS-Ag85a-IL-17a给药后，脾脏中的Th1细胞计数、BALF以及脾细胞和纵隔淋巴结上清液中的Th1细胞因子水平以及肺组织中的T-bet mRNA均显着增加。同时，rMS-Ag85a-IL-17a疫苗接种显着降低了BALF以及脾细胞和纵隔淋巴结上清液中Th2细胞计数、Th2细胞因子和Th17细胞因子水平以及肺组织中趋化因子mRNA表达。这些数据证实重组耻垢分枝杆菌在体内可以诱导IL-17A自身抗体，从而减轻哮喘气道炎症。
Asthma is a chronic inflammatory disorder, previous studies have shown that IL-17A contributes to the development of asthma, and there is a positive correlation between the level of IL-17A and the severity of disease. Here, we constructed recombinant Mycobacterium smegmatis expressing fusion protein Ag85A-IL-17A (rMS-Ag85a-IL-17a) and evaluated whether it could attenuate allergic airway inflammation, and further investigated the underlying mechanism. In this work, the murine model of asthma was established with ovalbumin, and mice were intranasally vaccinated with rMS-Ag85a-IL-17a. Autoantibody of IL-17A in sera was detected, and the airway inflammatory cells infiltration, the local cytokines and chemokines production and the histopathological changes of lung tissue were investigated. We found that the administration of rMS-Ag85a-IL-17a induced the autoantibody of IL-17A in sera. The vaccination of rMS-Ag85a-IL-17a remarkably reduced the infiltration of inflammatory cells and the secretion of mucus in lung tissue and significantly decreased the numbers of the total cells, eosinophils and neutrophils in BALF. Th1 cells count in spleen, Th1 cytokine levels in BALF and supernatant of splenocytes and mediastinal lymph nodes, and T-bet mRNA in lung tissue were significantly increased with rMS-Ag85a-IL-17a administration. Meanwhile, rMS-Ag85a-IL-17a vaccination markedly decreased Th2 cells count, Th2 cytokine and Th17 cytokine levels in BALF and supernatant of splenocytes and mediastinal lymph nodes, and chemokines mRNA expression in lung tissue. These data confirmed that recombinant Mycobacterium smegmatis in vivo could induce autoantibody of IL-17A, which attenuated asthmatic airway inflammation.