Polarization of type 1 macrophages is associated with the severity of viral encephalitis caused by japanese encephalitis virus and dengue virus

Ming Kai Jhan, Chia Ling Chen, Ting Jing Shen, Po Chun Tseng, Yung Ting Wang, Rahmat Dani Satria, Chia Yi Yu, Chiou Feng Lin

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Infection with flaviviruses causes mild to severe diseases, including viral hemorrhagic fever, vascular shock syndrome, and viral encephalitis. Several animal models explore the pathogenesis of viral encephalitis, as shown by neuron destruction due to neurotoxicity after viral infection. While neuronal cells are injuries caused by inflammatory cytokine production following microglial/macrophage activation, the blockade of inflammatory cytokines can reduce neurotoxicity to improve the survival rate. This study investigated the involvement of macrophage phenotypes in facilitating CNS inflammation and neurotoxicity during flavivirus infection, including the Japanese encephalitis virus, dengue virus (DENV), and Zika virus. Mice infected with different flaviviruses presented encephalitis-like symptoms, including limbic seizure and paralysis. Histology indicated that brain lesions were identified in the hippocampus and surrounded by mononuclear cells. In those regions, both the infiltrated macrophages and resident microglia were significantly increased. RNA-seq analysis showed the gene profile shifting toward type 1 macrophage (M1) polarization, while M1 markers validated this phenomenon. Pharmacologically blocking C-C chemokine receptor 2 and tumor necrosis factor-α partly retarded DENV-induced M1 polarization. In summary, flavivirus infection, such as JEV and DENV, promoted type 1 macrophage polarization in the brain associated with encephalitic severity.

Original languageEnglish
Article number3181
JournalCells
Volume10
Issue number11
DOIs
Publication statusPublished - Nov 2021

Keywords

  • Dengue virus
  • Encephalitis
  • Flavivirus
  • Macrophage
  • Polarization

ASJC Scopus subject areas

  • Medicine(all)

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