Background

Neutrophils are the most abundant cell type infiltrating the airways during severe respiratory syncytial virus (RSV) infection. Their exact role in disease pathophysiology remains enigmatic. Therefore, we determined genome-wide RNA expression profiles of local and systemic neutrophils in RSV bronchiolitis to provide further insight into local neutrophil biology.

Methods

We performed a single-center analysis, in 16 infants, admitted to the pediatric intensive care unit with severe RSV bronchiolitis. Neutrophils were isolated from blood and tracheobronchial aspirates (sputum). After low input RNA sequencing, differential expression of genes was determined followed by gene set analysis.

Results

Paired transcriptomic analysis of airway versus blood neutrophils showed an inflammatory phenotype, characterized by NF-kB signaling and upregulated expression of IL-6 and interferon pathways. We observed distinct expression of neutrophil activation genes (TNFSF13B, FCER1G).

Discussion

Our data indicate that airway neutrophils regulate their function at the transcriptional level in response to viral infection. It also suggests that local interferon drives the neutrophil response of severe RSV bronchiolitis.

中文翻译：

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气道中性粒细胞的转录组揭示了威胁生命的呼吸道合胞病毒感染中的干扰素反应。

背景

中性粒细胞是严重呼吸道合胞病毒（RSV）感染期间渗透到气道中的最丰富的细胞类型。它们在疾病病理生理中的确切作用仍然是个谜。因此，我们确定了RSV细支气管炎中局部和全身中性粒细胞的全基因组RNA表达谱，以提供对局部中性粒细胞生物学的进一步了解。

方法

我们对16例重症RSV毛细支气管炎的小儿重症监护病房的婴儿进行了单中心分析。从血液和气管支气管抽吸物中分离出嗜中性粒细胞。在低输入RNA测序后，确定基因的差异表达，然后进行基因组分析。

结果

气道对血液中性粒细胞的配对转录组分析显示了炎性表型，其特征在于NF-kB信号传导和IL-6和干扰素途径的表达上调。我们观察到嗜中性粒细胞激活基因（TNFSF13B，FCER1G）的独特表达。

讨论区

我们的数据表明，气道中性粒细胞在转录水平上响应病毒感染而调节其功能。这也表明局部干扰素可驱动严重RSV细支气管炎的中性粒细胞反应。