Effective treatment of allergic airway inflammation with Helicobacter pylori immunomodulators requires BATF3-dependent dendritic cells and IL-10
Effective treatment of allergic airway inflammation with Helicobacter pylori immunomodulators requires BATF3-dependent dendritic cells and IL-10
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DOI：
10.1073/pnas.1410579111
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发表时间：
2014-08-12
影响因子：
11.1
通讯作者：
Mueller, Anne
中科院分区：
文献类型：
--
作者：
Engler, Daniela B.;Reuter, Sebastian;Mueller, Anne
在发达国家的大部分地区，过敏性哮喘和其他特应性疾病的流行已达到流行病的程度。人类本土微生物群的逐渐丧失被认为是造成这一趋势的原因。细菌病原体幽门螺杆菌是正常胃微生物群的组成部分，其存在与人类和实验模型中的过敏和哮喘呈负相关。在这里我们展示了口头或IP。幽门螺杆菌提取物的耐受性可以防止气道高反应性、支气管肺泡嗜酸性粒细胞增多、肺部炎症和 Th2 细胞因子的产生，这些都是小鼠过敏原诱发哮喘的标志。哮喘保护作用不是由其他肠道病原体的提取物赋予的，而是需要热敏性幽门螺杆菌成分和 DC 固有的 IL-10 产生。基本亮氨酸拉链 ATF 样 3 (BATF3) 依赖性 CD103(+)CD11b(-) 树突状细胞谱系在受保护小鼠的肺部富集，是保护所必需的。两种幽门螺杆菌持久性决定因子，γ-谷氨酰转肽酶 GGT 和空泡细胞毒素 VacA，对于哮喘保护是必需的且足够的，并且可以以纯化形式施用以预防哮喘。总之，我们为幽门螺杆菌的免疫调节特性可用于旨在预防过敏原诱发的哮喘的耐受策略这一概念提供了临床前证据。
The prevalence of allergic asthma and other atopic diseases has reached epidemic proportions in large parts of the developed world. The gradual loss of the human indigenous microbiota has been held responsible for this trend. The bacterial pathogen Helicobacter pylori is a constituent of the normal gastric microbiota whose presence has been inversely linked to allergy and asthma in humans and experimental models. Here we show that oral or i.p. tolerization with H. pylori extract prevents the airway hyperresponsiveness, bronchoalveolar eosinophilia, pulmonary inflammation, and Th2 cytokine production that are hallmarks of allergen-induced asthma in mice. Asthma protection is not conferred by extracts from other enteropathogens and requires a heat-sensitive H. pylori component and the DC-intrinsic production of IL-10. The basic leucine zipper ATF-like 3 (BATF3)-dependent CD103(+)CD11b(-)dendritic cell lineage is enriched in the lungs of protected mice and strictly required for protection. Two H. pylori persistence determinants, the gamma-glutamyl-transpeptidase GGT and the vacuolating cytotoxin VacA, are required and sufficient for asthma protection and can be administered in purified form to prevent asthma. In conclusion, we provide preclinical evidence for the concept that the immunomodulatory properties of H. pylori can be exploited for tolerization strategies aiming to prevent allergen-induced asthma.