Wisconsin Infant Study Cohort (WISC)

项目总结/摘要 儿童病毒性呼吸道疾病（VRI）的发病率和社会成本是惊人的， 呼吸道疾病猖獗。在寻求预防这些常见和重要疾病的过程中， 也许解决办法就在农场。威斯康星州婴儿研究队列（WISC）的初步结果 研究表明，在农场长大的儿童VRI和特应性皮炎减少， 生命早期的细胞成熟轨迹。此外，在我们的初步研究中， 新生儿（高微生物暴露，低过敏率）具有更成熟的表型， 与WISC新生儿相比。总的来说，这些发现支持了我们的中心假设：农场- 相关的微生物暴露与免疫细胞成熟的增加、病毒感染的减少、 呼吸道疾病的严重程度，并降低过敏性。为了解决这个假设，我们将招募 我们目前招募了204名WISC参与者（93名农场参与者，111名非农场参与者），并招募了额外的Amish，WISC农场， 和WISC非农业家庭（50/组）。我们的研究有三个目标，采用尖端技术， 利用我们的调查团队在农业医学、出生队列、呼吸道病毒学方面的丰富经验， 和儿童的免疫发育。目的1：描述与农场相关的暴露与免疫相关性的关系 早期生活的发展。我们假设，农场相关的微生物暴露将促使先天性 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，我们将确定农业和微生物对免疫发育的关键细胞（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起作用。 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病率。我们 假设接触农场的婴儿减少了VRI负担并降低了对常见病毒的敏感性 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：确定与农场有关的 环境和生活方式因素，微生物暴露和定植（鼻咽和粪便），免疫 发展和临床结局（呼吸系统疾病负担和AD和过敏性致敏的发生率）。我们 假设来自农场家庭，特别是阿米什家庭房屋灰尘具有更多样的环境 微生物群落，鼻咽和肠道的微生物定植更多样化， 呼吸系统健康结果。在这些研究中，微生物基因组学将被用于识别细菌和真菌， 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开发新的战略， 增强生命早期的免疫发育，以实现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.