RNA sequencing of nasal lavage samples from mock- and Streptococcus pneumoniae-infected infant and adult mice

Acute respiratory infections (ARI), which generally begin with colonization of the mucosal surfaces of the upper respiratory tract (URT), are a leading cause of morbidity and mortality with the highest rate in infants. As a common colonizer of the URT, and one of the most prevalent causes of life-threatening infections in the pediatric population, Streptococcus pneumoniae (Spn) was used as a model pathogen to investigate the effect of age during URT infection. We used RNA-sequencing to transcriptionally profile and compare the mucosal epithelia of infant and adult mice at baseline (mock-infected) and during Spn infection. Analysis of the screen revealed an age-dependent alteration of genes involved in mucosal defense mechanisms that included dampened expression of ubiquitous antimicrobial molecules and tight junction proteins in infant mice compared to adults. These results demonstrate a window of vulnerability during postnatal development when altered mucosal barrier function may facilitate bacterial colonization and invasion. Overall design: We performed gene expression profiling of the nasal epithelium and associated tissue from mock- and Streptococcus pneumoniae-infected infant and adult mice, with a n=5 per group.

急性呼吸道感染（Acute respiratory infections, ARI）通常以上呼吸道（upper respiratory tract, URT）黏膜定植为起始，是引发发病与死亡的主要原因之一，在婴幼儿群体中发病率最高。作为上呼吸道常见定植菌，同时也是儿科人群中危及生命感染的最主要致病菌之一，肺炎链球菌（Streptococcus pneumoniae, Spn）被选为模式病原菌，用以探究上呼吸道感染过程中的年龄相关影响。我们采用RNA测序技术，对基线状态（模拟感染，mock-infected）以及肺炎链球菌感染状态下的婴幼儿与成年小鼠的黏膜上皮细胞进行转录组分析并开展对比研究。对该筛选的分析结果显示，黏膜防御机制相关基因存在年龄依赖性改变：与成年小鼠相比，婴幼儿小鼠体内普遍存在的抗菌分子与紧密连接蛋白的表达水平显著下调。本研究结果揭示了出生后发育阶段存在一段易感窗口期，此时黏膜屏障功能异常可能会促进细菌定植与侵袭。实验整体设计：我们对模拟感染组与肺炎链球菌感染组的婴幼儿及成年小鼠的鼻上皮及其附属组织进行了基因表达谱分析，每组设置5个生物学重复（n=5）。