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Ex Vivo Host Transcriptomics During Cryptococcus neoformans, Cryptococcus gattii, and Candida albicans Infection of Peripheral Blood Mononuclear Cells From South African Volunteers
The Journal of Infectious Diseases ( IF 5.0 ) Pub Date : 2024-08-19 , DOI: 10.1093/infdis/jiae410 Ronan M Doyle 1 , Shichina Kannambath 2, 3 , Alan Pittman 3 , Rene Goliath 4 , Vinod Kumar 5 , Graeme Meintjes 4 , James Milburn 1, 5 , Mihai G Netea 6 , Thomas S Harrison 3, 7 , Joseph N Jarvis 1, 5 , Tihana Bicanic 3
The Journal of Infectious Diseases ( IF 5.0 ) Pub Date : 2024-08-19 , DOI: 10.1093/infdis/jiae410 Ronan M Doyle 1 , Shichina Kannambath 2, 3 , Alan Pittman 3 , Rene Goliath 4 , Vinod Kumar 5 , Graeme Meintjes 4 , James Milburn 1, 5 , Mihai G Netea 6 , Thomas S Harrison 3, 7 , Joseph N Jarvis 1, 5 , Tihana Bicanic 3
Affiliation
Cryptococcus neoformans, Cryptococcus gattii, and Candida albicans are opportunistic fungal pathogens associated with infections in immunocompromised hosts. Cryptococcal meningitis (CM) is the leading fungal cause of human immunodeficiency virus–related deaths globally, with the majority occurring in Africa. The human immune response to C albicans infection has been studied extensively in large genomics studies whereas cryptococcal infections, despite their severity, are comparatively understudied. Here we investigated the transcriptional response of immune cells after in vitro stimulation with in vitro C neoformans, C gattii, and C albicans infection of peripheral blood mononuclear cells collected from healthy South African volunteers. We found a lower transcriptional response to cryptococcal stimuli compared to C albicans and unique expression signatures from all 3 fungal stimuli. This work provides a starting point for further studies comparing the transcriptional signature of CM in immunocompromised patients, with the goal of identifying biomarkers of disease severity and possible novel treatment targets.
中文翻译:
来自南非志愿者的外周血单核细胞的新型隐球菌、格特隐球菌和白色念珠菌感染期间的离体宿主转录组学
新型隐球菌、格特隐球菌和白色念珠菌是与免疫功能低下宿主感染相关的机会性真菌病原体。隐球菌性脑膜炎 (CM) 是全球人类免疫缺陷病毒相关死亡的主要真菌原因,其中大多数发生在非洲。人类对白色念珠菌感染的免疫反应已在大型基因组学研究中进行了广泛研究,而隐球菌感染尽管严重,但研究相对不足。在这里,我们研究了从健康南非志愿者收集的外周血单核细胞的体外新型隐形芽孢杆菌、格特隐形体和白色念珠菌感染体外刺激后免疫细胞的转录反应。我们发现与白色念珠菌相比,对隐球菌刺激的转录反应较低,并且所有 3 种真菌刺激都具有独特的表达特征。这项工作为进一步研究比较免疫功能低下患者 CM 的转录特征提供了一个起点,目的是确定疾病严重程度的生物标志物和可能的新治疗靶点。
更新日期:2024-08-19
中文翻译:
来自南非志愿者的外周血单核细胞的新型隐球菌、格特隐球菌和白色念珠菌感染期间的离体宿主转录组学
新型隐球菌、格特隐球菌和白色念珠菌是与免疫功能低下宿主感染相关的机会性真菌病原体。隐球菌性脑膜炎 (CM) 是全球人类免疫缺陷病毒相关死亡的主要真菌原因,其中大多数发生在非洲。人类对白色念珠菌感染的免疫反应已在大型基因组学研究中进行了广泛研究,而隐球菌感染尽管严重,但研究相对不足。在这里,我们研究了从健康南非志愿者收集的外周血单核细胞的体外新型隐形芽孢杆菌、格特隐形体和白色念珠菌感染体外刺激后免疫细胞的转录反应。我们发现与白色念珠菌相比,对隐球菌刺激的转录反应较低,并且所有 3 种真菌刺激都具有独特的表达特征。这项工作为进一步研究比较免疫功能低下患者 CM 的转录特征提供了一个起点,目的是确定疾病严重程度的生物标志物和可能的新治疗靶点。