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Abstract：
Cryptococcal meningitis (CM) is a severe fungal disease in immunocompromised patients affecting the central nervous system (CNS). Host response and immunological alterations in the cerebrospinal fluid (CSF) after invasion of Cryptococcus neoformans to the central nervous system have been investigated before but rigorous and comprehensive studies examining cellular changes in the CSF of patients with cryptococccal meningitis are still rare. We retrospectively collected CSF analysis and flow cytometry data of CSF and blood in patients with CM (n = 7) and compared them to HIV positive patients without meningitis (n = 13) and HIV negative healthy controls (n = 7). Within the group of patients with CM we compared those with HIV infection (n = 3) or other immunocompromised conditions (n = 4). Flow cytometry analysis revealed an elevation of natural killer cells and natural killer T cells in the CSF and blood of HIV negative patients with CM, pointing to innate immune activation in early stages after fungal invasion. HIV positive patients with CM exhibited stronger blood-CSF-barrier disruption. Follow-up CSF analysis over up to 150 days showed heterogeneous cellular courses in CM patients with slow normalization of CSF after induction of antifungal therapy.
摘要：
隐球菌性脑膜炎（CM）是影响中枢神经系统（CNS）的免疫功能低下患者的严重真菌病。以前已经研究了新生隐球菌入侵中枢神经系统后脑脊液（CSF）的宿主反应和免疫学改变，但是严格而全面的研究隐球菌性脑膜炎患者CSF细胞变化的研究仍然很少。我们回顾性收集了CM患者（n=7）的CSF分析和CSF和血液的流式细胞术数据，并将其与无脑膜炎的HIV阳性患者（n=13）和HIV阴性健康对照（n=7）进行了比较。在CM患者组中，我们比较了HIV感染（n=3）或其他免疫受损疾病（n=4）的患者。流式细胞术分析显示HIV阴性CM患者的CSF和血液中自然杀伤细胞和自然杀伤T细胞升高，指向真菌入侵后早期的先天免疫激活。患有CM的HIV阳性患者表现出更强的血液CSF屏障破坏。长达150天的后续CSF分析显示，CM患者在诱导抗真菌治疗后CSF缓慢正常化的细胞过程不均匀。
