Open AccessDynamic Changes of Microglia/Macrophage M 1 and M 2 Polarization in T heiler's Murine Encephalomyelitis
Author(s) -
Herder Vanessa,
Iskandar Cut Dahlia,
Kegler Kristel,
Hansmann Florian,
Elmarabet Suliman Ahmed,
Khan Muhammad Akram,
Kalkuhl Arno,
Deschl Ulrich,
Baumgärtner Wolfgang,
Ulrich Reiner,
Beineke Andreas
Publication year - 2015
Publication title -
brain pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.986
H-Index - 132
eISSN - 1750-3639
pISSN - 1015-6305
DOI - 10.1111/bpa.12238
Subject(s) - microglia , myelin , remyelination , biology , encephalomyelitis , immunology , macrophage polarization , experimental autoimmune encephalomyelitis , inflammation , multiple sclerosis , pathology , microbiology and biotechnology , macrophage , central nervous system , medicine , neuroscience , biochemistry , in vitro
Microglia and macrophages play a central role for demyelination in T heiler's murine encephalomyelitis ( TME ) virus infection, a commonly used infectious model for chronic‐progressive multiple sclerosis. In order to determine the dynamic changes of microglia/macrophage polarization in TME , the spinal cord of Swiss Jim Lambert ( SJL ) mice was investigated by gene expression profiling and immunofluorescence. Virus persistence and demyelinating leukomyelitis were confirmed by immunohistochemistry and histology. Electron microscopy revealed continuous myelin loss together with abortive myelin repair during the late chronic infection phase indicative of incomplete remyelination. A total of 59 genes out of 151 M 1‐ and M 2‐related genes were differentially expressed in TME virus‐infected mice over the study period. The onset of virus‐induced demyelination was associated with a dominating M 1 polarization, while mounting M 2 polarization of macrophages/microglia together with sustained prominent M 1‐related gene expression was present during the chronic‐progressive phase. Molecular results were confirmed by immunofluorescence, showing an increased spinal cord accumulation of CD 16/32 + M 1‐, arginase‐1 + M 2‐ and Y m1 + M 2‐type cells associated with progressive demyelination. The present study provides a comprehensive database of M 1‐/ M 2‐related gene expression involved in the initiation and progression of demyelination supporting the hypothesis that perpetuating interaction between virus and macrophages/microglia induces a vicious circle with persistent inflammation and impaired myelin repair in TME .