Author:
Stoff Melanie,Ebbecke Tim,Ciurkiewicz Malgorzata,Pavasutthipaisit Suvarin,Mayer-Lambertz Sabine,Störk Theresa,Pavelko Kevin D.,Baumgärtner Wolfgang,Jung Klaus,Lepenies Bernd,Beineke Andreas
Abstract
AbstractNeurotropic viruses target the brain and contribute to neurologic diseases. C-type lectin receptors (CLRs) are pattern recognition receptors that recognize carbohydrate structures on endogenous molecules and pathogens. The myeloid CLR dendritic cell immunoreceptor (DCIR) is expressed by antigen presenting cells and mediates inhibitory intracellular signalling. To investigate the effect of DCIR on neurotropic virus infection, mice were infected experimentally with Theiler’s murine encephalomyelitis virus (TMEV). Brain tissue of TMEV-infected C57BL/6 mice and DCIR−/− mice were analysed by histology, immunohistochemistry and RT-qPCR, and spleen tissue by flow cytometry. To determine the impact of DCIR deficiency on T cell responses upon TMEV infection in vitro, antigen presentation assays were utilised. Genetic DCIR ablation in C57BL/6 mice was associated with an ameliorated hippocampal integrity together with reduced cerebral cytokine responses and reduced TMEV loads in the brain. Additionally, absence of DCIR favoured increased peripheral cytotoxic CD8+ T cell responses following TMEV infection. Co-culture experiments revealed that DCIR deficiency enhances the activation of antigen-specific CD8+ T cells by virus-exposed dendritic cells (DCs), indicated by increased release of interleukin-2 and interferon-γ. Results suggest that DCIR deficiency has a supportive influence on antiviral immune mechanisms, facilitating virus control in the brain and ameliorates neuropathology during acute neurotropic virus infection.
Funder
Deutsche Forschungsgemeinschaft
Stiftung Tierärztliche Hochschule Hannover (TIHO)
Publisher
Springer Science and Business Media LLC
Cited by
1 articles.
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1. Immune Functions of Astrocytes in Viral Neuroinfections;International Journal of Molecular Sciences;2023-02-09