Host Respiratory Transcriptome Signature Associated with Poor Outcome in Children with Influenza-Staphylococcus aureus Pneumonia.

Host Respiratory Transcriptome Signature Associated with Poor Outcome in Children with Influenza-Staphylococcus aureus Pneumonia.
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宿主呼吸转录组特征与流感金黄色葡萄球菌肺炎儿童的不良结局相关。

DOI:
10.1093/infdis/jiac325
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发表时间:
2022
期刊:
The Journal of infectious diseases
影响因子:
--
通讯作者:
Moffitt,KristinL
Moffitt,KristinL
中科院分区:
--
文献类型:
--
作者:
Britto,Carl;Mohorianu,Irina;Yeung,Tracy;Cheung,Elaine;Novak,Tanya;Hall,MarkW;Mourani,PeterM;Weiss,ScottL;Thomas,NealJ;Markovitz,Barry;Randolph,AdrienneG;Moffitt,KristinL

文献摘要

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流感与金黄色葡萄球菌的呼吸道合并感染常引起严重疾病;耐甲氧西林 S.金黄色葡萄球菌 (MRSA) 合并感染通常是致命的。了解疾病发病机制可以为治疗提供信息。我们的目的是鉴定患有 S 型流感危重儿科患者呼吸区的宿主和病原体转录组(信使 RNA)特征。金黄色葡萄球菌感染(ISAC),预测更糟糕结果的特征。对从气管内抽吸样品中提取的信使 RNA 进行了评估。金黄色葡萄球菌和宿主转录组生物特征。流感-MRSA 结果更差,但 190S 的结果更差。与金黄色葡萄球菌毒力相关的基因,6个在MRSA共感染者与甲氧西林敏感者之间表达存在差异。金黄色葡萄球菌合并感染的患者,并且没有歧视性的结果。将 ISAC 患者的宿主基因表达与仅感染流感的患者进行比较。临床结果较差(死亡或长期多器官功能障碍)的患者干扰素表达相对减少,干扰素γ诱导的免疫细胞趋化剂CXCL10和CXCL11下调。在 ISAC 中,气道宿主而非病原体基因表达谱预测了更差的临床结果。
Respiratory coinfection of influenza withStaphylococcus aureusoften causes severe disease; methicillin-resistantS. aureus(MRSA) coinfection is frequently fatal. Understanding disease pathogenesis may inform therapies. We aimed to identify host and pathogen transcriptomic (messenger RNA) signatures from the respiratory compartment of pediatric patients critically ill with influenza–S. aureuscoinfection (ISAC), signatures that predict worse outcomes. Messenger RNA extracted from endotracheal aspirate samples was evaluated forS. aureusand host transcriptomic biosignatures. Influenza-MRSA outcomes were worse, but of 190S. aureusvirulence-associated genes, 6 were differentially expressed between MRSA-coinfected versus methicillin-susceptibleS. aureus–coinfected patients, and none discriminated outcome. Host gene expression in patients with ISAC was compared with that in patients with influenza infection alone. Patients with poor clinical outcomes (death or prolonged multiorgan dysfunction) had relatively reduced expression of interferons and down-regulation of interferon γ–induced immune cell chemoattractants CXCL10 and CXCL11. In ISAC, airway host but not pathogen gene expression profiles predicted worse clinical outcomes.