Artikel
Interleukin-10 receptor blockade enhances neuroinflammation in Theiler’s murine encephalomyelitis
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Veröffentlicht: | 25. August 2015 |
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Gliederung
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Introduction: Theiler’s murine encephalomyelitis (TME) serves as an important model for acute and chronic infectious disorders of the central nervous system (CNS). In the present study the influence of interleukin (IL)-10 pathway modulation upon neuropathology was investigated in TME virus-infected SJL mice.
Materials and methods: Five week old SJL mice were intracerebrally infected with TME virus and treated with IL-10 receptor-blocking antibodies (anti-IL-10R Ab) or isotype control. At necropsy brains and spinal cords were examined by histology, immunohistochemistry and reverse transcriptase polymerase chain reaction. Phenotypical changes in lymphoid organs were determined by flow cytometry.
Results: Infected SJL mice with and without anti-IL-10R Ab treatment developed early acute encephalitis and demyelinating leukomyelitis. Immunohistochemistry revealed an increased infiltration of CD3+ T cells in the hippocampus of IL-10R blocked animals at 7 dpi. Moreover, neuronal loss characterized by reduction of NeuN+ cells was found in the pyramidal cell layer associated with an increased number of beta-amyloid precursor protein-expressing axons in the stratum radiatum following receptor blockade. Despite enhanced inflammation in the central nervous system no differences of the viral load were observed between both groups.
Conclusions: IL-10R blockade leads to enhanced virus-induced immunopathology with neuronal loss and axonopathy. Results demonstrate the pivotal role of IL-10 for immune homeostasis and neuroprotection in infectious CNS disorders.