Young age is a risk factor for respiratory and gastrointestinal infections. Here, we compared infant and adult mice to identify age-dependent mechanisms that drive susceptibility to mucosal infections during early life. Transcriptional profiling of the upper respiratory tract (URT) epithelium revealed significant dampening of early life innate mucosal defenses. Epithelial-mediated production of the most abundant antimicrobial molecules, lysozyme, and lactoferrin, and the polymeric immunoglobulin receptor (pIgR), responsible for IgA transcytosis, was expressed in an age-dependent manner. This was attributed to delayed functional development of serous cells. Absence of epithelial-derived lysozyme and the pIgR was also observed in the small intestine during early life. Infection of infant mice with lysozyme-susceptible strains of Streptococcus pneumoniae or Staphylococcus aureus in the URT or gastrointestinal tract, respectively, demonstrated an age-dependent regulation of lysozyme enzymatic activity. Lysozyme derived from maternal milk partially compensated for the reduction in URT lysozyme activity of infant mice. Similar to our observations in mice, expression of lysozyme and the pIgR in nasopharyngeal samples collected from healthy human infants during the first year of life followed an age-dependent regulation. Thus, a global pattern of reduced antimicrobial and IgA-mediated defenses may contribute to increased susceptibility of young children to mucosal infections.

年轻是呼吸道和胃肠道感染的危险因素。在这里，我们比较了婴儿和成年小鼠，以确定年龄依赖性机制，这些机制会在生命早期导致对粘膜感染的易感性。上呼吸道 (URT) 上皮细胞的转录分析显示生命早期的先天粘膜防御显着减弱。上皮介导的最丰富的抗菌分子、溶菌酶和乳铁蛋白以及负责 IgA 转胞吞作用的聚合免疫球蛋白受体 (pIgR) 的产生以年龄依赖性方式表达。这归因于浆液细胞的功能发育延迟。在生命早期的小肠中也观察到上皮来源的溶菌酶和 pIgR 的缺失。用溶菌酶敏感菌株感染幼鼠URT 或胃肠道中的肺炎链球菌或金黄色葡萄球菌分别证明了溶菌酶酶活性的年龄依赖性调节。来自母乳的溶菌酶部分补偿了幼鼠 URT 溶菌酶活性的降低。与我们在小鼠中的观察结果类似，在生命的第一年从健康人类婴儿收集的鼻咽样本中溶菌酶和 pIgR 的表达遵循年龄依赖性调节。因此，抗菌和 IgA 介导的防御能力下降的全球模式可能导致幼儿对粘膜感染的易感性增加。