早产儿和足月儿对呼吸道合胞病毒 A 的抗病毒反应差异。

Differential anti-viral response to respiratory syncytial virus A in preterm and term infants.

机构信息

Infection, Immunity and Global Health, Murdoch Children's Research Institute, Melbourne, Australia; Department of Paediatrics, University of Melbourne, Melbourne, Australia.

出版信息

EBioMedicine. 2024 Apr;102:105044. doi: 10.1016/j.ebiom.2024.105044. Epub 2024 Mar 6.

DOI:10.1016/j.ebiom.2024.105044

PMID:38447274

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10933467/

Abstract

BACKGROUND

Preterm infants are more likely to experience severe respiratory syncytial virus (RSV) disease compared to term infants. The reasons for this are multi-factorial, however their immature immune system is believed to be a major contributing factor.

METHODS

We collected cord blood from 25 preterm (gestational age 30.4-34.1 weeks) and 25 term infants (gestation age 37-40 weeks) and compared the response of cord blood mononuclear cells (CBMCs) to RSVA and RSVB stimulation using neutralising assays, high-dimensional flow cytometry, multiplex cytokine assays and RNA-sequencing.

FINDINGS

We found that preterm and term infants had similar maternally derived neutralising antibody titres to RSVA and RSVB. Preterm infants had significantly higher myeloid dendritic cells (mDC) RSV infection compared to term infants. Differential gene expression analysis of RSVA stimulated CBMCs revealed enrichment of genes involved in cytokine production and immune regulatory pathways involving IL-10, IL-36γ, CXCL1, CXCL2, SOCS1 and SOCS3 in term infants, while differentially expressed genes (DEGs) in preterm infants were related to cell cycle (CDK1, TTK, ESCO2, KNL1, CDC25A, MAD2L1) without associated expression of immune response genes. Furthermore, enriched genes in term infants were highly correlated suggesting an increased co-ordination of their immune response to RSVA. When comparing DEGs in preterm and term infants following RSVB stimulation, no differences in immune response genes were identified.

INTERPRETATION

Overall, our data suggests that preterm infants have a more restricted immunological response to RSVA compared with term infants. While further studies are required, these findings may help to explain why preterm infants are more susceptible to severe RSV disease and identify potential therapeutic targets to protect these vulnerable infants.

FUNDING

Murdoch Children's Research Institute Infection and Immunity theme grant.

摘要

背景

与足月儿相比，早产儿更有可能经历严重的呼吸道合胞病毒（RSV）疾病。其原因是多方面的，但他们不成熟的免疫系统被认为是一个主要的促成因素。

方法

我们收集了 25 名早产儿（胎龄 30.4-34.1 周）和 25 名足月儿（胎龄 37-40 周）的脐血，并使用中和测定、高维流式细胞术、多重细胞因子测定和 RNA 测序比较了脐血单核细胞（CBMC）对 RSV-A 和 RSV-B 刺激的反应。

发现

我们发现早产儿和足月儿对 RSV-A 和 RSV-B 的母体来源中和抗体滴度相似。与足月儿相比，早产儿的髓样树突状细胞（mDC） RSV 感染明显更高。RSVA 刺激的 CBMC 的差异基因表达分析显示，与 IL-10、IL-36γ、CXCL1、CXCL2、SOCS1 和 SOCS3 等细胞因子产生和免疫调节途径相关的基因在足月儿中富集，而早产儿中的差异表达基因（DEGs）与细胞周期（CDK1、TTK、ESCO2、KNL1、CDC25A、MAD2L1）相关，而与免疫反应基因无关。此外，足月儿中富集的基因高度相关，表明其对 RSV-A 的免疫反应协调性增强。比较 RSV-B 刺激后早产儿和足月儿的 DEGs 时，未发现免疫反应基因的差异。