Latent murine cytomegalovirus infection contributes to EAE pathogenesis

© 2014 University of Kragujevac, Faculty of Science. All rights reserved. Viral infection has been identifi ed as the most likely environmental trigger of multiple sclerosis (MS). Th ere are confl icting data regarding the role of cytomegalovirus (CMV) in MS pathogenesis. We utilised experimental autoimmune encephalomyelitis (EAE)-resistant BALB/c mice and murine cytomegalovirus (MCMV), the murine homolog of CMV, to examine the mechanism by which viral infection enhances autoimmune neuroinfl ammation. Mice subjected to latent neonatal MCMV infection developed the typical characteristics of EAE. Similar to MS, the MCMV-infected EAE-induced mice developed infi ltrates in the central nervous system (CNS) composed of similar percentages of CD4+ and CD8+ T cells. Th e infl ux of both Th 1 and Th 17 cells into the CNS of MCMV-infected EAE-induced mice was observed. Interestingly, the development of autoimmune neuroinfl ammation after latent MCMV infection was accompanied by a signifi cant infl ux of Tc17 cells (CD8+IL-17+ and CD8+RoRγt+) but not Tc1, cells. Our results suggest that latent MCMV infection aff ects the development of infl ammatory lymphocytes that exhibit encephalitogenic potential, thereby mediating increased CNS pathology following EAE induction, and that CMV represents a possible environmental factor in the pathogenesis of MS and other autoimmune diseases

Murine cytomegalovirus infection induces susceptibility to EAE in resistant BALB/c mice

© 2017 Milovanovic, Popovic, Milovanovic, Kvestak, Arsenijevic, Stojanovic, Tanaskovic, Krmpotic, Arsenijevic, Jonjic and Lukic. In contrast to C57BL/6 mice, BALB/c mice are relatively resistant to the induction of experimental autoimmune encephalomyelitis (EAE) after challenge with MOG35-55 peptide. Here, we provide the first evidence that infection with murine cytomegalovirus (MCMV) in adulthood abrogates this resistance. Infected BALB/c mice developed clinical and histological signs similar to those seen in susceptible C57BL/6 mice. In addition to CD4+ cells, large proportion of cells in the infiltrate of diseased BALB/c mice was CD8+, similar with findings in multiple sclerosis. CD8+ cells that responded to ex vivo restimulation with MOG35-55 were not specific for viral epitopes pp89 and m164. MCMV infection favors proinflammatory type of dendritic cells (CD86+CD40+CD11c+) in the peripheral lymph organs, M1 type of microglia in central nervous system, and increases development of Th1/Th17 encephalitogenic cells. This study indicates that MCMV may enhance autoimmune neuropathology and abrogate inherent resistance to EAE in mouse strain by enhancing proinflammatory phenotype of antigen-presenting cells, Th1/Th17, and CD8 response to MOG35-55