Abstract
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.
Highlights
Multiple sclerosis (MS) is a chronic inflammatory, demyelinating disease of the central nervous system (CNS) with axonal injury, characterized by varying clinical course, pathology, and inflammatory patterns [1]
BALB/c mice immunized with MOG35–55 did not develop clinical signs of EAE, while BALB/c mice infected with murine cytomegalovirus (MCMV) 8 weeks after birth and 10 days later challenged with MOG35–55 in CFA and pertussis toxin (MCMV + MOG35–55) developed clinical signs that correspond to EAE manifestations seen in C57BL/6 mice (Figure 1A)
Infiltration in CNS of MCMV + MOG35–55, expressed by mean histological score (Figure 1D) and total cell number (Figure 1C), was significantly higher compared with BALB/c mice immunized with MOG35–55 only mice
Summary
Multiple sclerosis (MS) is a chronic inflammatory, demyelinating disease of the central nervous system (CNS) with axonal injury, characterized by varying clinical course, pathology, and inflammatory patterns [1]. It develops in susceptible hosts after interaction with environmental factors which trigger the disease by promoting the activation of myelin-specific T cells that normally circulate in the peripheral lymph organs of all individuals [2]. Epstein–Barr virus (EBV) has been mostly associated with increased MS risk [5] It has been shown increased CD8+ T cell response to EBV lytic antigens in active MS and in relapses [6]. Infection with murine gamma herpesvirus 68 (γHV-68), the murine homolog to EBV, polarizes the adaptive immune response and heightens CNS pathology following experimental autoimmune encephalomyelitis (EAE) induction and likely, influences MS pathogenesis [7]
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