Innate immune response in neuronopathic forms of Gaucher disease confers resistance against viral-induced encephalitis

Acta Neuropathologica Communications

Ziv Klausner¹  Deborah E. Rothbard²  Anthony H. Futerman²  Tomer Israely³  Roy Avraham³  Noam Erez³  Sharon Melamed³  Einat B. Vitner³  Nir Paran³ 

[1] Department of Applied Mathematics, Israel Institute for Biological Research;Department of Biomolecular Sciences, Weizmann Institute of Science;Department of Infectious Diseases, Israel Institute for Biological Research;

关键词: Gaucher’s disease;    Alphaviruses;    Sindbis virus;    Encephalitis;    Glucosylceramide;    Brain inflammation;   

DOI  :  10.1186/s40478-020-01020-6

来源: DOAJ

【 摘 要 】

Abstract Both monogenic diseases and viral infections can manifest in a broad spectrum of clinical phenotypes that range from asymptomatic to lethal, suggesting that other factors modulate disease severity. Here, we examine the interplay between the genetic neuronopathic Gaucher’s disease (nGD), and neuroinvasive Sindbis virus (SVNI) infection. Infection of nGD mice with SVNI had no influence on nGD severity. However, nGD mice were more resistant to SVNI infection. Significantly different inflammatory responses were seen in nGD brains when compared with SVNI brains: the inflammatory response in the nGD brains consisted of reactive astrocytes and microglia with no infiltrating macrophages, but the inflammatory response in the brains of SVNI-infected mice was characterized by infiltration of macrophages and altered activation of microglia and astrocytes. We suggest that the innate immune response activated in nGD confers resistance against viral infection of the CNS.

【 授权许可】

Unknown