Tsujimura Yusuke, Inada Hiroyasu, Yoneda Misao, Fujita Tomoyuki, Matsuo Kazuhiro, Yasutomi Yasuhiro
Laboratory of Immunoregulation and Vaccine Research, Tsukuba Primate Research Center, National Institute of Biomedical Innovation, Tsukuba, Ibaraki, Japan.
Department of Pharmaceutical Sciences, Suzuka University of Medical Science, Suzuka, Mie, Japan.
PLoS One. 2014 Sep 5;9(9):e106807. doi: 10.1371/journal.pone.0106807. eCollection 2014.
Many epidemiological studies have suggested that the recent increase in prevalence and severity of allergic diseases such as asthma is inversely correlated with Mycobacterium bovis bacillus Calmette Guerin (BCG) vaccination. However, the underlying mechanisms by which mycobacterial components suppress allergic diseases are not yet fully understood. Here we showed the inhibitory mechanisms for development of allergic airway inflammation by using highly purified recombinant Ag85B (rAg85B), which is one of the major protein antigens secreted from M. tuberculosis. Ag85B is thought to be a single immunogenic protein that can elicit a strong Th1-type immune response in hosts infected with mycobacteria, including individuals vaccinated with BCG. Administration of rAg85B showed a strong inhibitory effect on the development of allergic airway inflammation with induction of Th1-response and IL-17and IL-22 production. Both cytokines induced by rAg85B were involved in the induction of Th17-related cytokine-production innate immune cells in the lung. Administration of neutralizing antibodies to IL-17 or IL-22 in rAg85B-treated mice revealed that IL-17 induced the infiltration of neutrophils in BAL fluid and that allergen-induced bronchial eosinophilia was inhibited by IL-22. Furthermore, enhancement of the expression of genes associated with tissue homeostasis and wound healing was observed in bronchial tissues after rAg85B administration in a Th17-related cytokine dependent manner. The results of this study provide evidence for the potential usefulness of rAg85B as a novel approach for anti-allergic effect and tissue repair other than the role as a conventional TB vaccine.
许多流行病学研究表明，近期哮喘等过敏性疾病的患病率和严重程度上升与卡介苗（BCG）接种呈负相关。然而，分枝杆菌成分抑制过敏性疾病的潜在机制尚未完全明确。在此，我们使用高度纯化的重组Ag85B（rAg85B）（结核分枝杆菌分泌的主要蛋白质抗原之一）展示了过敏性气道炎症发展的抑制机制。Ag85B被认为是一种单一的免疫原性蛋白质，可在感染分枝杆菌的宿主（包括接种卡介苗的个体）中引发强烈的Th1型免疫反应。给予rAg85B对过敏性气道炎症的发展具有强烈的抑制作用，并诱导Th1反应以及IL-17和IL-22的产生。rAg85B诱导的这两种细胞因子均参与肺中Th17相关细胞因子产生的固有免疫细胞的诱导。在rAg85B处理的小鼠中给予IL-17或IL-22的中和抗体表明，IL-17诱导中性粒细胞在BAL液中浸润，而IL-22抑制变应原诱导的支气管嗜酸性粒细胞增多。此外，以Th17相关细胞因子依赖的方式给予rAg85B后，在支气管组织中观察到与组织稳态和伤口愈合相关基因的表达增强。本研究结果为rAg85B作为一种新型抗过敏和组织修复方法（而非传统结核病疫苗的作用）的潜在用途提供了证据。
