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<p>Neurotropic viruses infect the central nervous system (CNS) and can cause severe neurological disorders. Theiler’s murine encephalomyelitis virus (TMEV) infection in C57BL/6 mice serves as a model for virus-induced encephalitis and hippocampal damage. C-type lectin domain family 12 member A (CLEC12A) is an inhibitory receptor, which modulates immune responses during inflammatory processes. However, the role of CLEC12A during neurotropic virus infections remains unclear. In this study, CLEC12A-deficient (CLEC12A<sup>−/−</sup>) and wild type C57BL/6 mice were infected with TMEV. Neuroinflammatory responses, viral load, and immune cell infiltration were analyzed using immunohistochemistry, RT-qPCR, and flow cytometry. CLEC12A<sup>−/−</sup> mice exhibited increased T cell sequestration in the brain, along with a higher expression of pro-inflammatory cytokine (<i>TNF-α</i>, <i>IL-1β</i>) and antigen presentation genes (<i>CD11c</i>, <i>CD80</i>, <i>MHC-I</i>) during acute infection. This led to an improved viral clearance in the hippocampus. CLEC12A deficiency also activates splenic CD4<sup>+</sup> T cells and CD8<sup>+</sup> cytotoxic T cells upon infection. Despite increased peripheral T cell activation and neuroinflammation, CLEC12A<sup>−/−</sup> mice displayed less hippocampal damage with improved neuronal and axonal integrity. In conclusion, CLEC12A signaling in C57BL/6 mice contributes to suppressive immune modulation, delaying viral elimination and exacerbating brain damage during acute neurotropic virus infection.</p>

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CLEC12A signaling represses protective immune responses and contributes to hippocampal pathology in neurotropic picornavirus infection

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月10日

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  • M. K. Ameen,
  • M. Stoff,
  • S. Pavasutthipaisit,
  • T. Ebbecke,
  • M. Ciurkiewicz,
  • T. Störk,
  • J. Ruland,
  • B. Lepenies,
  • A. Beineke

摘要

Neurotropic viruses infect the central nervous system (CNS) and can cause severe neurological disorders. Theiler’s murine encephalomyelitis virus (TMEV) infection in C57BL/6 mice serves as a model for virus-induced encephalitis and hippocampal damage. C-type lectin domain family 12 member A (CLEC12A) is an inhibitory receptor, which modulates immune responses during inflammatory processes. However, the role of CLEC12A during neurotropic virus infections remains unclear. In this study, CLEC12A-deficient (CLEC12A−/−) and wild type C57BL/6 mice were infected with TMEV. Neuroinflammatory responses, viral load, and immune cell infiltration were analyzed using immunohistochemistry, RT-qPCR, and flow cytometry. CLEC12A−/− mice exhibited increased T cell sequestration in the brain, along with a higher expression of pro-inflammatory cytokine (TNF-α, IL-1β) and antigen presentation genes (CD11c, CD80, MHC-I) during acute infection. This led to an improved viral clearance in the hippocampus. CLEC12A deficiency also activates splenic CD4+ T cells and CD8+ cytotoxic T cells upon infection. Despite increased peripheral T cell activation and neuroinflammation, CLEC12A−/− mice displayed less hippocampal damage with improved neuronal and axonal integrity. In conclusion, CLEC12A signaling in C57BL/6 mice contributes to suppressive immune modulation, delaying viral elimination and exacerbating brain damage during acute neurotropic virus infection.