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Updated: May 18, 2026
Induction of Experimental Autoimmune Encephalomyelitis in Mice and Evaluation of the Disease-dependent Distribution of Immune Cells in Various Tissues
Published on: May 8, 2016
Theiler's murine encephalomyelitis virus induced phenotype switch of microglia in vitro
I Gerhauser1, F Hansmann, C Puff
1Department of Pathology, University of Veterinary Medicine Hannover, Bünteweg 17, D-30559 Hannover, Germany. Ingo.Gerhauser@tiho-hannover.de
Abstract:
The present in vitro study aimed to define the involvement of astrocytes and microglia in the initial inflammatory response of Theiler's murine encephalomyelitis (TME), a virus-induced mouse model of multiple sclerosis, and whether intralesional microglia exert pro- (M1) or anti-inflammatory (M2) effects following TME virus (TMEV) infection. Therefore astrocytes and microglia were purified from neonatal murine brains and inoculated either with TMEV or mock-solution. Gene expression of IL-1, IL-2, IL-10, IL-12, TNF, TNF receptors (TNFR1, TNFR2), TGFβ1, IFNγ and transcription factors NF-κB (p50, p65) and AP-1 (c-jun, c-fos) were quantified using RT-qPCR at 6, 48, and 240h post infection (hpi). In addition, IL-1, IL-10, IL-12, TNF and TGFβ1 mRNA transcripts were investigated at 168 hpi in TMEV- and mock-infected SJL/J mice. Overall in vitro astrocytes showed a significant higher amount of viral RNA compared to microglia. In addition, TMEV-infected astrocytes showed higher numbers of IL-1, IL-12 and TNF transcripts at 48 hpi. In microglia high IL-10 and low IL-12 mRNA levels were detected at 48 hpi, while the opposite was the case at 240 hpi. In addition, TNF mRNA was increased in microglia at 240 hpi. In addition, the observed up-regulation of IL-1, IL-12 and IL-10 in the early phase of TME in vivo substantiates the relevance of these cytokines during the disease induction. Summarized data indicate that TMEV infection of microglia induces a switch from the anti-inflammatory (M2) during the early phase to the pro-inflammatory (M1) phenotype in the later phase of the infection. The simultaneous expression of TNF and its receptors by both cell types might generate autocrine feedback loops possibly associated with pro-inflammatory actions of astrocytes via TNFR1.
Insights
Theiler
Area of Science:
- Neuroimmunology
- Virology
- Cellular Immunology
Background:
- Theiler's murine encephalomyelitis (TME) is a virus-induced model for multiple sclerosis.
- Astrocytes and microglia are key glial cells involved in neuroinflammation.
Purpose of the Study:
- To investigate the role of astrocytes and microglia in the early inflammatory response to Theiler's murine encephalomyelitis virus (TMEV).
- To determine if microglia adopt pro-inflammatory (M1) or anti-inflammatory (M2) phenotypes during TMEV infection.
Main Methods:
- Primary astrocyte and microglia cultures were infected with TMEV or a mock solution.
- Gene expression of cytokines (IL-1, IL-10, IL-12, TNF, TGFβ1, IFNγ) and transcription factors (NF-κB, AP-1) was quantified using RT-qPCR.
- In vivo analysis of cytokine mRNA in TMEV-infected mice.
Main Results:
- Astrocytes showed higher viral RNA and increased IL-1, IL-12, and TNF transcripts post-infection.
- Microglia exhibited a shift from high IL-10/low IL-12 early on to low IL-10/high IL-12 later, with increased TNF at 240 hpi.
- In vivo data confirmed early upregulation of IL-1, IL-12, and IL-10.
Conclusions:
- TMEV infection induces distinct inflammatory responses in astrocytes and microglia.
- Microglia transition from an anti-inflammatory (M2) to a pro-inflammatory (M1) phenotype during TMEV infection.
- TNF signaling may contribute to astrocyte-mediated inflammation via autocrine feedback loops.
