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

Sharon Melamed, Roy Avraham, Deborah E Rothbard, Noam Erez, Tomer Israely, Ziv Klausner, Anthony H Futerman, Nir Paran, Einat B Vitner

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number144
Number of pages20
JournalActa Neuropathologica Communications
Volume8
DOIs
StatePublished - 24 Aug 2020

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