House dust exposure mediates gut microbiome Lactobacillus enrichment and airway immune defense against allergens and virus infection
House dust exposure mediates gut microbiome Lactobacillus enrichment and airway immune defense against allergens and virus infection
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DOI：
10.1073/pnas.1310750111
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发表时间：
2014-01-14
影响因子：
11.1
通讯作者：
Lynch, Susan V.
中科院分区：
文献类型：
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作者：
Fujimura, Kei E.;Demoor, Tine;Lynch, Susan V.
在婴儿早期暴露于狗已被证明可以降低儿童过敏性疾病发展的风险，养狗与明显的室内灰尘微生物暴露有关。在这里，我们证明，使用小鼠模型，小鼠暴露于狗相关的室内灰尘保护卵清蛋白或蟑螂过敏原介导的气道病变。受保护的动物表现出气道T细胞总数的显著减少，Th 2相关气道反应的下调，以及粘蛋白分泌。在与狗相关的粉尘暴露之后，受保护动物的盲肠微生物组被广泛地重组，其中包括约氏乳杆菌的显著富集。野生型动物补充L. johnsonii保护它们免受气道变应原攻击或呼吸道合胞病毒感染。L. johnsonii介导的保护作用与活化的CD 11 c（+）/CD 11b（+）和CD 11 c（+）/CD 8（+）细胞的总数和比例显著降低以及气道Th 2细胞因子表达显著降低相关。我们的研究结果表明，暴露于与狗相关的家庭灰尘导致对气道过敏原挑战的保护和独特的胃肠道微生物组组成。此外，本研究还鉴定了L. johnsonii是胃肠道内的关键物种，能够以保护免受各种呼吸损伤的方式影响远端粘膜表面的适应性免疫。
Exposure to dogs in early infancy has been shown to reduce the risk of childhood allergic disease development, and dog ownership is associated with a distinct house dust microbial exposure. Here, we demonstrate, using murine models, that exposure of mice to dog-associated house dust protects against ovalbumin or cockroach allergen-mediated airway pathology. Protected animals exhibited significant reduction in the total number of airway T cells, down-regulation of Th2-related airway responses, as well as mucin secretion. Following dog-associated dust exposure, the cecal microbiome of protected animals was extensively restructured with significant enrichment of, amongst others, Lactobacillus johnsonii. Supplementation of wild-type animals with L. johnsonii protected them against both airway allergen challenge or infection with respiratory syncytial virus. L. johnsonii-mediated protection was associated with significant reductions in the total number and proportion of activated CD11c(+)/CD11b(+) and CD11c(+)/CD8(+) cells, as well as significantly reduced airway Th2 cytokine expression. Our results reveal that exposure to dog-associated household dust results in protection against airway allergen challenge and a distinct gastrointestinal microbiome composition. Moreover, the study identifies L. johnsonii as a pivotal species within the gastrointestinal tract capable of influencing adaptive immunity at remote mucosal surfaces in a manner that is protective against a variety of respiratory insults.