Wisconsin Infant Study Cohort (WISC)

项目摘要/摘要 儿童病毒性呼吸道疾病(VRI)的发病率和社会成本令人震惊，而且是过敏性的 呼吸道疾病十分猖獗。在寻找预防这些常见和重要疾病的过程中， 也许解决方案就在农场里。威斯康星州婴儿研究队列(WISC)的初步结果 证明在农场长大的孩子减少了VRI和特应性皮炎，并具有明显的先天免疫力 细胞在生命早期的成熟轨迹。此外，在我们的初步研究中，来自阿米什人的单个核细胞 新生儿(高微生物暴露，低过敏率)具有更成熟的表型和增强的抗病毒能力 与WISC新生儿的反应相比较。总体而言，这些发现支持我们的中心假设：农场- 相关微生物暴露与免疫细胞成熟度增加、病毒减少有关 呼吸系统疾病的严重程度，并降低过敏反应。为了解决这一假设，我们将征募 我们目前招收了204名WISC参与者(93个农场，111个非农场)，并招募了更多的阿米什人、WISC农场、 和武钢非农家庭(50户/组)。我们的研究有三个目标，利用尖端技术和 利用我们调查团队在农场医学、出生队列、呼吸道病毒学方面的丰富经验 以及儿童的免疫发育。目标1：描述与农场相关的暴露与免疫的关系 在生命早期的发展。我们假设，与农场相关的微生物暴露将促使先天增加 免疫细胞在生命早期的成熟和功能，包括增强的抗炎机制。在这些 研究，我们将确定养殖和微生物对关键细胞(上皮细胞， 浆细胞样树突状细胞、中性粒细胞、T调节细胞)在粘膜对病毒和过敏原的反应中。 目的2：确定农场暴露如何影响VRI的负担和过敏性疾病的发生率。我们 假设接触农场的婴儿减少了VRI的负担，并降低了对常见疾病的敏感度 环境过敏原。在这些研究中，我们将使用病毒诊断来确定感染和疾病， 并测量对空气过敏原的特异性IgE。目标3：定义与农场相关的群体之间的特定关联 环境和生活方式因素、微生物暴露和定植(鼻咽和粪便)、免疫 发展和临床结果(呼吸道疾病负担、AD和过敏性敏感率)。我们 假设来自农场家庭，特别是阿米什家庭的房屋灰尘具有更多样化的环境 微生物群落，鼻咽和肠道中更多样化的微生物定植，并得到改善 呼吸系统健康结果。在这些研究中，微生物基因组学将被用来识别细菌和真菌 家庭灰尘、鼻咽和肠道样本，我们将分析与免疫模式的关系 发育、VRI和过敏。这些研究的完成将导致制定新的战略 加强生命早期免疫发育，实现对VRI和过敏性疾病的一级预防。

PROJECT SUMMARY/ABSTRACT The morbidity and cost to society from childhood viral respiratory illnesses (VRI) is staggering, and allergic respiratory disease is rampant. In the search for prevention for these common and important diseases, perhaps the solutions are on the farm. Preliminary results from the Wisconsin Infant Study Cohort (WISC) demonstrate that children raised on farms have reduced VRI and atopic dermatitis, and distinct innate immune cell maturation trajectories in early life. Furthermore, in our preliminary studies mononuclear cells from Amish newborns (high microbial exposure, low rates of allergy) had a more mature phenotype and enhanced antiviral responses compared to WISC newborns. Collectively, these findings support our central hypothesis: farm- related microbial exposures are associated with increased immune cell maturation, decreased viral respiratory illness severity, and decreased allergic sensitization. To address this hypothesis, we will enlist our currently enrolled 204 WISC participants (93 farm, 111 non-farm), and enroll additional Amish, WISC farm, and WISC non-farm families (50/group). Our study has three aims that employ cutting-edge technologies and leverage our investigative team's extensive experience with farm medicine, birth cohorts, respiratory virology and immune development in children. Aim 1: To characterize how farm-related exposures relate to immune development in early life. We hypothesize that farm-related microbial exposures will prompt increased innate immune cell maturation and function in early life, including enhanced anti-inflammatory mechanisms. In these studies, we will identify farming and microbial effects on immune development of key cells (epithelial cell, plasmacytoid dendritic cell, neutrophil, Tregulatory cells) in the mucosal response to viruses and allergens. Aim 2: To determine how farm exposures affect the burden of VRI and rates of allergic diseases. We hypothesize that farm-exposed infants have reduced VRI burden and reduced sensitization to common environmental allergens. In these studies, we will use viral diagnostics to determine infections and illnesses, and measure specific IgE to aeroallergens. Aim 3: To define group-specific associations between farm-related environmental and lifestyle factors, microbial exposure and colonization (nasopharyngeal and stool), immune development, and clinical outcomes (respiratory illness burden and rates of AD and allergic sensitization). We hypothesize that house dust from farm homes, particularly Amish households, has more diverse environmental microbiota communities, more diverse microbial colonization of the nasopharynx and gut, and improved respiratory health outcomes. In these studies, microbial genomics will be used to identify bacteria and fungi in household dust, nasopharynx, and gut samples, and we will analyze relationships with patterns of immune development, VRI, and allergy. Completion of these studies will lead to development of novel strategies for enhancing immune development in early life to achieve primary prevention of VRI and allergic diseases.