Kassaza Kennedy, Wasswa Fredrickson B, Nielsen Kirsten, Bazira Joel
Department of Microbiology and Parasitology, Mbarara University of Science and Technology, Mbarara, UGA.
Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Blacksburg, USA.
Cureus. 2025 Jul 7;17(7):e87404. doi: 10.7759/cureus.87404. eCollection 2025 Jul.
Cryptococcal meningitis (CM) remains a major cause of mortality among people living with human immunodeficiency virus (HIV), especially in sub-Saharan Africa. The interplay between fungal genotype and host immune response is critical in determining disease outcome. We conducted ex vivo cytokine profiling using peripheral blood from HIV-positive and HIV-negative adults stimulated with heat-inactivated whole-cell antigens from two strains: the reference strain H99 and the genetically distinct UgCl377 clinical strain. These strains differ at multiple loci, including the CNAG_04922 gene. Luminex-based quantification revealed that H99 induced significantly higher levels of CD40-ligand, IL-10, IL-12p70, IL-13, IL-15, and IL-33. These cytokines reflect pro-inflammatory, Th2, and regulatory responses, suggesting robust immune activation. In contrast, the UgCl377 strain elicited a dampened cytokine profile. While this study does not isolate the effect of CNAG_04922 alone, it demonstrates that whole-cell antigens from genetically distinct strains of elicit differential cytokine responses. These findings provide a foundation for future mechanistic studies using purified proteins or isogenic strains.
隐球菌性脑膜炎（CM）仍然是人类免疫缺陷病毒（HIV）感染者死亡的主要原因，尤其是在撒哈拉以南非洲地区。真菌基因型与宿主免疫反应之间的相互作用对于决定疾病转归至关重要。我们使用来自HIV阳性和HIV阴性成年人的外周血进行了体外细胞因子分析，这些外周血用来自两株热灭活全细胞抗原刺激：参考菌株H99和基因不同的UgCl377临床菌株。这些菌株在多个位点存在差异，包括CNAG_04922基因。基于Luminex的定量分析显示，H99诱导的CD40配体、IL-10、IL-12p70、IL-13、IL-15和IL-33水平显著更高。这些细胞因子反映了促炎、Th2和调节反应，表明有强大的免疫激活。相比之下，UgCl377菌株引发的细胞因子反应较弱。虽然这项研究没有单独分离出CNAG_04922的作用，但它表明来自基因不同菌株的全细胞抗原会引发不同的细胞因子反应。这些发现为未来使用纯化蛋白或同基因菌株进行机制研究奠定了基础。
