Hu Yang, Wang Dong, Zhai Kan, Tong Zhaohui
1 Department of Respiratory Medicine and Critical Care Medicine, and.
2 Department of Medical Research Center, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.
Am J Respir Cell Mol Biol. 2017 Mar;56(3):322-331. doi: 10.1165/rcmb.2015-0356OC.
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 down-regulation 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.
肺孢子菌肺炎（PCP）是一种机会性传染病，在免疫抑制宿主中普遍存在。对于人类免疫缺陷病毒阴性的PCP患者，皮质类固醇治疗是最主要的危险因素，尽管对于皮质类固醇如何改变宿主对肺孢子菌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测接受皮质类固醇治疗的PCP小鼠肺部的免疫反应。结果显示，与天然免疫相关的基因，如抗原加工与呈递、炎症反应和吞噬作用，以及B和T淋巴细胞免疫相关基因均下调。对应于B细胞免疫的基因表达抑制很突出，包括B细胞信号传导、内环境稳定和免疫球蛋白产生。这一发现通过对PCP患者小鼠肺部和外周血进行定量PCR得到证实。流式细胞术也显示，接受皮质类固醇治疗 的PCP小鼠中B细胞显著减少。我们的研究强调，皮质类固醇治疗会抑制PCP宿主中的B细胞免疫，这可能是皮质类固醇治疗会促使PCP病情发展的主要原因之一。
