Journal Article

DKFZ-2025-02362

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png CLEC12A signaling represses protective immune responses and contributes to hippocampal pathology in neurotropic picornavirus infection.

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

2025
Springer Nature [London]

Abstract: 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.

Keyword(s): Antiviral immunity ; C-type lectin receptor ; CLEC12A ; Hippocampal pathology ; Neuroinflammation ; TMEV

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Contributing Institute(s):

1. DKTK Koordinierungsstelle München (MU01)

Research Program(s):

1. 899 - ohne Topic (POF4-899) (POF4-899)

Appears in the scientific report 2025

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