PDF(Pubmed)
Abstract：
Respiratory syncytial virus is the major cause of acute lower respiratory tract infections in young children, causing extensive mortality and morbidity globally, with limited therapeutic or preventative options. Cathelicidins are innate immune antimicrobial host defence peptides and have antiviral activity against RSV. However, upper respiratory tract cathelicidin expression and the relationship with host and environment factors in early life, are unknown. Infant cohorts were analysed to characterise early life nasal cathelicidin levels, revealing low expression levels in the first week of life, with increased levels at 9 months which are comparable to 2-year-olds and healthy adults. No impact of prematurity on nasal cathelicidin expression was observed, nor were there effects of sex or birth mode, however, nasal cathelicidin expression was lower in the first week-of-life in winter births. Nasal cathelicidin levels were positively associated with specific inflammatory markers and demonstrated to be associated with microbial community composition. Importantly, levels of nasal cathelicidin expression were elevated in infants with mild RSV infection, but, in contrast, were not upregulated in infants hospitalised with severe RSV infection. These data suggest important relationships between nasal cathelicidin, upper airway microbiota, inflammation, and immunity against RSV infection, with interventional potential.
摘要：
呼吸道合胞病毒是幼儿急性下呼吸道感染的主要原因,在全球范围内造成广泛的死亡率和发病率，有限的治疗或预防选择。Cathelicidins是先天性免疫抗微生物宿主防御肽，具有抗RSV的抗病毒活性。然而,早期上呼吸道导管素的表达及其与宿主和环境因素的关系,是未知的。对婴儿队列进行了分析，以表征生命早期的鼻导管素水平，在生命的第一周显示低表达水平，在9个月时水平升高，与2岁儿童和健康成年人相当。未观察到早产儿对鼻导管素表达的影响，也没有性别或出生模式的影响，然而,在冬季出生的第一周，鼻导管素的表达较低。鼻导管素水平与特定的炎症标志物呈正相关，并证明与微生物群落组成相关。重要的是,轻度RSV感染婴儿的鼻导管素表达水平升高，但是,相比之下,在严重RSV感染住院的婴儿中没有上调。这些数据表明鼻导管素之间的重要关系，上呼吸道微生物群，炎症,和对RSV感染的免疫力，具有介入潜力。
