Wannemacher Rouven, Stegmann Felix, Eikelberg Deborah, Bühler Melanie, Li Dandan, Kohale Sayali Kalidas, Asawapattanakul Thanaporn, Ebbecke Tim, Raulf Marie-Kristin, Baumgärtner Wolfgang, Lepenies Bernd, Gerhauser Ingo
Department of Pathology, University of Veterinary Medicine Hannover, Foundation, Hannover, Germany.
Center for Systems Neuroscience Hannover, Hannover, Germany.
Front Immunol. 2025 Apr 9;16:1467207. doi: 10.3389/fimmu.2025.1467207. eCollection 2025.
A hallmark of many lysosomal storage diseases (LSD) is the alteration of immune responses, often starting before the onset of clinical disease. The present study aimed to investigate how G gangliosidosis impacted the course of an acute central nervous system (CNS) virus infection before the clinical onset of LSD.
For this purpose, and wildtype control mice (both C57BL/6 background) were intracerebrally infected with the BeAn strain of Theiler's murine encephalomyelitis virus (TMEV) at the age of 5 weeks and sacrificed 4, 7, 14 and 98 days post infection, respectively. Histology, immunohistochemistry, and flow cytometry was used to assess viral load and immune cell activation and infiltration.
Both wildtype and mice were able to clear the virus from the CNS and did not develop any clinical symptoms of TMEV-associated disease, thus indicating no overt alteration in susceptibility to TMEV infection. However, in the early phase post infection, mice displayed a slightly delayed T cell response as well as an increase in the number and activation of CNS microglia.
These results suggest that already in the early stage of disease (before clinical onset) G gangliosidosis causes an impaired T cell response and microglial hyperreactivity.
许多溶酶体贮积症（LSD）的一个标志是免疫反应的改变，这种改变通常在临床疾病发作之前就开始了。本研究旨在调查在LSD临床发作之前，G神经节苷脂沉积症如何影响急性中枢神经系统（CNS）病毒感染的病程。
为此，将 和野生型对照小鼠（均为C57BL/6背景）在5周龄时脑内接种泰勒氏鼠脑脊髓炎病毒（TMEV）的BeAn株，并分别在感染后4、7、14和98天处死。采用组织学、免疫组织化学和流式细胞术评估病毒载量以及免疫细胞的活化和浸润情况。
野生型和 小鼠均能够从CNS清除病毒，且未出现任何TMEV相关疾病的临床症状，因此表明对TMEV感染的易感性没有明显改变。然而，在感染后的早期阶段， 小鼠表现出T细胞反应略有延迟以及CNS小胶质细胞数量和活化增加。
这些结果表明，在疾病的早期阶段（临床发作之前），G神经节苷脂沉积症就会导致T细胞反应受损和小胶质细胞反应过度。
