Transcriptomic Analysis Reveals Significant B Lymphocyte Suppression in Corticosteroid-Treated Hosts with Pneumocystis Pneumonia
Transcriptomic Analysis Reveals Significant B Lymphocyte Suppression in Corticosteroid-Treated Hosts with Pneumocystis Pneumonia
复制标题
转录组分析显示，经过皮质类固醇治疗的肺孢子虫肺炎宿主体内 B 淋巴细胞受到显着抑制。
DOI：
10.1165/rcmb.2015-0356oc
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发表时间：
2017-03-01
影响因子：
6.4
通讯作者：
Tong, Zhaohui
中科院分区：
文献类型：
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作者：
Hu, Yang;Wang, Dong;Tong, Zhaohui
肺孢子虫肺炎（PCP）是一种机会性感染性疾病，在免疫抑制的宿主中流行。皮质类固醇治疗是人类免疫缺陷病毒阴性的PCP患者最重要的风险因素，尽管人们对皮质类固醇如何改变宿主对肺孢子虫感染的防御知之甚少。在本研究中，我们使用转录组分析来检查皮质类固醇治疗的PCP小鼠肺部的免疫反应。结果显示，与天然免疫相关的基因，如抗原加工和呈递，炎症反应和吞噬作用，以及B和T淋巴细胞免疫相关的基因下调。对应于B细胞免疫的基因表达的抑制，包括B细胞信号传导、稳态和IG产生，是显著的。这一发现得到了小鼠肺和PCP患者外周血定量PCR的证实。流式细胞术还显示皮质类固醇治疗的PCP小鼠中B细胞显著耗竭。我们的研究强调，皮质类固醇治疗会抑制PCP宿主的B细胞免疫，这可能是皮质类固醇治疗可能刺激PCP发展的主要原因之一。
Pneumocystis pneumonia (PCP) is an opportunistic, infectious disease that is prevalent in immunosuppressed hosts. Corticosteroid treatment is the most significant risk factor for patients with PCP who are human immunodeficiency virus negative, although little is known about how corticosteroids alter the host defense against Pneumocystis infection. In the present study, we used transcriptome analysis to examine the immune response in the lungs of corticosteroid-treated PCP mice. The results showed downregulation in the genes related to both native immunity, such as antigen processing and presentation, inflammatory response, and phagocytosis, as well as B and T lymphocyte immunity. The repression of gene expression, corresponding to B cell immunity, including B cell signaling, homeostasis, and Ig production, was prominent. The finding was confirmed by quantitative PCR of mouse lungs and the peripheral blood of patients with PCP. Flow cytometry also revealed a significant depletion of B cells in corticosteroid-treated PCP mice. Our study has highlighted that corticosteroid treatment suppresses the B cell immunity in the PCP host, which is likely one of the main reasons that corticosteroid treatment may stimulate PCP development.