Turturice Benjamin A, Ranjan Ravi, Nguyen Brian, Hughes Lauren M, Andropolis Kalista E, Gold Diane R, Litonjua Augusto A, Oken Emily, Perkins David L, Finn Patricia W
1 Department of Microbiology and Immunology.
2 Division of Pulmonary, Critical Care, Sleep, and Allergy, and.
Am J Respir Cell Mol Biol. 2017 Oct;57(4):419-427. doi: 10.1165/rcmb.2017-0027OC.
There is a high prevalence of aeroallergen sensitivity in asthmatic populations, and seroreactivity to aeroallergens early in infancy is associated with increased risk of developing asthma later in life. In addition to allergen sensitivity, asthma development has been associated with differential microbial exposure and infection in early life. We have previously shown that cord blood mononuclear cells respond to common aeroallergens (i.e., house dust mite [Der f1] and cockroach [Bla g2]) as assayed by lymphoproliferation and cytokine (IL-13 and IFN-γ) production. We hypothesized that there is a relationship between perinatal microbial exposure and response to specific aeroallergens. To test this hypothesis, we isolated DNA from cord blood serum samples with known lymphoproliferative and cytokine responses to Bla g2 and Der f1. Bacterial 16S ribosomal DNA amplicon libraries were generated and analyzed using high throughput sequencing of cord blood serum samples. In our analysis, we identified major compositional differences, including diversity and abundance of specific taxa, between groups whose IL-13 response to Der f1 and Bla g2 differed. We demonstrate a strong association between the ratio of Acinetobacter to Proteobacteria and IL-13 production and the probability of IL-13 production after allergen exposure. IL-13 concentrations in serum were also significantly correlated with the diversity of bacterial DNA. Together, these results underscore the relationship between immune responses to allergens and bacterial exposure during perinatal development.
哮喘患者群体中对空气过敏原敏感的情况很普遍,婴儿期早期对空气过敏原的血清反应性与日后患哮喘风险增加有关。除了过敏原敏感性外,哮喘的发生还与生命早期不同的微生物接触和感染有关。我们之前已经表明,脐血单个核细胞对常见空气过敏原(即屋尘螨[Der f1]和蟑螂[Bla g2])有反应,这通过淋巴细胞增殖和细胞因子(IL-13和IFN-γ)产生来测定。我们假设围产期微生物接触与对特定空气过敏原的反应之间存在关联。为了验证这一假设,我们从对Bla g2和Der f1有已知淋巴细胞增殖和细胞因子反应的脐血血清样本中分离DNA。使用脐血血清样本的高通量测序生成并分析细菌16S核糖体DNA扩增子文库。在我们的分析中,我们确定了对Der f1和Bla g2的IL-13反应不同的组之间的主要组成差异,包括特定分类群的多样性和丰度。我们证明不动杆菌与变形菌的比例与IL-13产生以及过敏原暴露后IL-13产生的概率之间存在密切关联。血清中的IL-13浓度也与细菌DNA的多样性显著相关。总之,这些结果强调了围产期发育过程中对过敏原的免疫反应与细菌接触之间的关系。