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首页> 外文期刊>Scientific reports. >Modulation of Immune Signaling and Metabolism Highlights Host and Fungal Transcriptional Responses in Mouse Models of Invasive Pulmonary Aspergillosis
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Modulation of Immune Signaling and Metabolism Highlights Host and Fungal Transcriptional Responses in Mouse Models of Invasive Pulmonary Aspergillosis

机译：免疫信号和代谢的调制突出显示侵袭性肺曲霉病的小鼠模型中的宿主和真菌转录反应。

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Incidences of invasive pulmonary aspergillosis, an infection caused predominantly by Aspergillus fumigatus, have increased due to the growing number of immunocompromised individuals. While A. fumigatus is reliant upon deficiencies in the host to facilitate invasive disease, the distinct mechanisms that govern the host-pathogen interaction remain enigmatic, particularly in the context of distinct immune modulating therapies. To gain insights into these mechanisms, RNA-Seq technology was utilized to sequence RNA derived from lungs of 2 clinically relevant, but immunologically distinct murine models of IPA on days 2 and 3 post inoculation when infection is established and active disease present. Our findings identify notable differences in host gene expression between the chemotherapeutic and steroid models at the interface of immunity and metabolism. RT-qPCR verified model specific and nonspecific expression of 23 immune-associated genes. Deep sequencing facilitated identification of highly expressed fungal genes. We utilized sequence similarity and gene expression to categorize the A. fumigatus putative in vivo secretome. RT-qPCR suggests model specific gene expression for nine putative fungal secreted proteins. Our analysis identifies contrasting responses by the host and fungus from day 2 to 3 between the two models. These differences may help tailor the identification, development, and deployment of host- and/or fungal-targeted therapeutics.
机译：侵袭性肺曲霉病（主要由烟曲霉引起的感染）的发病率由于免疫功能低下个体的数量增加而增加。尽管烟曲霉依靠宿主的缺陷来促进侵袭性疾病，但是控制宿主-病原体相互作用的独特机制仍然是个谜，特别是在独特的免疫调节疗法的情况下。为了深入了解这些机制，RNA-Seq技术用于在感染后第2天和第3天建立感染并出现活动性疾病时，对来源于2种临床相关但免疫学上不同的IPA鼠模型的肺中的RNA进行测序。我们的发现确定了在免疫和代谢界面上化学疗法和类固醇模型之间宿主基因表达的显着差异。 RT-qPCR验证了23种免疫相关基因的模型特异性和非特异性表达。深度测序有助于鉴定高度表达的真菌基因。我们利用序列相似性和基因表达来对烟曲霉推定的体内分泌组进行分类。 RT-qPCR提出了九种推测的真菌分泌蛋白的模型特异性基因表达。我们的分析确定了两个模型在第2天到第3天之间宿主和真菌的对比反应。这些差异可以帮助定制针对宿主和/或真菌的治疗剂的鉴定，开发和部署。

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