Division of Infection, Immunity & Respiratory Medicine, University of Manchester, Manchester, UK.
Allergy Department, 2nd Pediatric Clinic, National and Kapodistrian University of Athens, Athens, Greece.
Allergy. 2023 May;78(5):1258-1268. doi: 10.1111/all.15634. Epub 2023 Jan 17.
From early life, respiratory viruses are implicated in the development, exacerbation and persistence of respiratory conditions such as asthma. Complex dynamics between microbial communities and host immune responses shape immune maturation and homeostasis, influencing health outcomes. We evaluated the hypothesis that the respiratory virome is linked to systemic immune responses, using peripheral blood and nasopharyngeal swab samples from preschool-age children in the PreDicta cohort.
Peripheral blood mononuclear cells from 51 children (32 asthmatics and 19 healthy controls) participating in the 2-year multinational PreDicta cohort were cultured with bacterial (Bacterial-DNA, LPS) or viral (R848, Poly:IC, RV) stimuli. Supernatants were analysed by Luminex for the presence of 22 relevant cytokines. Virome composition was obtained using untargeted high throughput sequencing of nasopharyngeal samples. The metagenomic data were used for the characterization of virome profiles and the presence of key viral families (Picornaviridae, Anelloviridae, Siphoviridae). These were correlated to cytokine secretion patterns, identified through hierarchical clustering and principal component analysis.
High spontaneous cytokine release was associated with increased presence of Prokaryotic virome profiles and reduced presence of Eukaryotic and Anellovirus profiles. Antibacterial responses did not correlate with specific viral families or virome profile; however, low antiviral responders had more Prokaryotic and less Eukaryotic virome profiles. Anelloviruses and Anellovirus-dominated profiles were equally distributed among immune response clusters. The presence of Picornaviridae and Siphoviridae was associated with low interferon-λ responses. Asthma or allergy did not modify these correlations.
Antiviral cytokine responses at a systemic level reflect the upper airway virome composition. Individuals with low innate interferon responses have higher abundance of Picornaviruses (mostly Rhinoviruses) and bacteriophages. Bacteriophages, particularly Siphoviridae, appear to be sensitive sensors of host antimicrobial capacity, while Anelloviruses are not correlated with TLR-induced immune responses.
从生命早期开始，呼吸道病毒就与哮喘等呼吸道疾病的发展、恶化和持续存在有关。微生物群落与宿主免疫反应之间的复杂动态关系塑造了免疫成熟和稳态，影响健康结果。我们评估了这样一个假设，即呼吸道病毒组与全身免疫反应有关，使用来自学前儿童 PreDicta 队列的外周血和鼻咽拭子样本。
来自参与为期 2 年的多国 PreDicta 队列的 51 名儿童（32 名哮喘患儿和 19 名健康对照者）的外周血单核细胞用细菌（细菌-DNA、LPS）或病毒（R848、Poly：IC、RV）刺激物进行培养。通过 Luminex 分析上清液中存在的 22 种相关细胞因子。使用鼻咽样本的非靶向高通量测序获得病毒组组成。对宏基因组数据进行分析，以确定病毒组谱和关键病毒家族（小核糖核酸病毒科、圆环病毒科、长尾病毒科）的存在。通过层次聚类和主成分分析，将这些与细胞因子分泌模式相关联。
高自发细胞因子释放与原核病毒组谱的存在增加和真核病毒组谱的存在减少相关。抗细菌反应与特定的病毒家族或病毒组谱无关；然而，低抗病毒反应者具有更多的原核和更少的真核病毒组谱。圆环病毒和圆环病毒主导的谱在免疫反应群中均匀分布。小核糖核酸病毒科和长尾病毒科的存在与低干扰素-λ反应相关。哮喘或过敏并未改变这些相关性。
全身抗病毒细胞因子反应反映上呼吸道病毒组组成。具有低先天干扰素反应的个体具有更高丰度的小核糖核酸病毒（主要是鼻病毒）和噬菌体。噬菌体，特别是长尾病毒科，似乎是宿主抗菌能力的敏感传感器，而圆环病毒与 TLR 诱导的免疫反应无关。
