Doyle Ronan M, Kannambath Shichina, Pittman Alan, Goliath Rene, Kumar Vinod, Meintjes Graeme, Milburn James, Netea Mihai G, Harrison Thomas S, Jarvis Joseph N, Bicanic Tihana
Department of Clinical Research, London School of Hygiene and Tropical Medicine.
Genomics Facility, The Institute of Cancer Research.
J Infect Dis. 2025 Feb 4;231(1):e254-e262. doi: 10.1093/infdis/jiae410.
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.
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病因,大多数死亡发生在非洲。在大型基因组学研究中,对人类针对白色念珠菌感染的免疫反应进行了广泛研究,而隐球菌感染尽管严重,但相对研究较少。在此,我们研究了从健康南非志愿者收集的外周血单核细胞经体外新型隐球菌、格特隐球菌和白色念珠菌感染后,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,且所有三种真菌刺激均有独特的表达特征。这项工作为进一步比较免疫功能低下患者中CM的转录特征提供了一个起点,目标是识别疾病严重程度的生物标志物和可能的新型治疗靶点。