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Article

CARD9 Deficiency Increases Hippocampal Injury Following Acute Neurotropic Picornavirus Infection but Does Not Affect Pathogen Elimination

1
Department of Pathology, University of Veterinary Medicine Hannover, 30559 Hannover, Germany
2
Center for Systems Neuroscience, 30559 Hannover, Germany
3
Department of Pathology, Faculty of Veterinary Medicine, Mahanakorn University of Technology, Bangkok 10530, Thailand
4
Institute for Immunology and Research Center for Emerging Infections and Zoonoses, University of Veterinary Medicine Hannover, 30559 Hannover, Germany
5
Department of Immunology, Mayo Clinic, Rochester, MN 55905, USA
*
Author to whom correspondence should be addressed.
These contributed equally first to this work.
These contributed equally last to this work.
Academic Editor: Asher Ornoy
Int. J. Mol. Sci. 2021, 22(13), 6982; https://doi.org/10.3390/ijms22136982
Received: 3 May 2021 / Revised: 20 June 2021 / Accepted: 25 June 2021 / Published: 29 June 2021
Neurotropic viruses target the brain and contribute to neurologic diseases. Caspase recruitment domain containing family member 9 (CARD9) controls protective immunity in a variety of infectious disorders. To investigate the effect of CARD9 in neurotropic virus infection, CARD9−/− and corresponding C57BL/6 wild-type control mice were infected with Theiler’s murine encephalomyelitis virus (TMEV). Brain tissue was analyzed by histology, immunohistochemistry and molecular analyses, and spleens by flow cytometry. To determine the impact of CARD9 deficiency on T cell responses in vitro, antigen presentation assays were utilized. Genetic ablation of CARD9 enhanced early pro-inflammatory cytokine responses and accelerated infiltration of T and B cells in the brain, together with a transient increase in TMEV-infected cells in the hippocampus. CARD9−/− mice showed an increased loss of neuronal nuclear protein+ mature neurons and doublecortin+ neuronal precursor cells and an increase in β-amyloid precursor protein+ damaged axons in the hippocampus. No effect of CARD9 deficiency was found on the initiation of CD8+ T cell responses by flow cytometry and co-culture experiments using virus-exposed dendritic cells or microglia-enriched glial cell mixtures, respectively. The present study indicates that CARD9 is dispensable for the initiation of early antiviral responses and TMEV elimination but may contribute to the modulation of neuroinflammation, thereby reducing hippocampal injury following neurotropic virus infection. View Full-Text
Keywords: Theiler’s murine encephalomyelitis virus; neurotropic virus; CARD9; hippocampal damage Theiler’s murine encephalomyelitis virus; neurotropic virus; CARD9; hippocampal damage
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MDPI and ACS Style

Pavasutthipaisit, S.; Stoff, M.; Ebbecke, T.; Ciurkiewicz, M.; Mayer-Lambertz, S.; Störk, T.; Pavelko, K.D.; Lepenies, B.; Beineke, A. CARD9 Deficiency Increases Hippocampal Injury Following Acute Neurotropic Picornavirus Infection but Does Not Affect Pathogen Elimination. Int. J. Mol. Sci. 2021, 22, 6982. https://doi.org/10.3390/ijms22136982

AMA Style

Pavasutthipaisit S, Stoff M, Ebbecke T, Ciurkiewicz M, Mayer-Lambertz S, Störk T, Pavelko KD, Lepenies B, Beineke A. CARD9 Deficiency Increases Hippocampal Injury Following Acute Neurotropic Picornavirus Infection but Does Not Affect Pathogen Elimination. International Journal of Molecular Sciences. 2021; 22(13):6982. https://doi.org/10.3390/ijms22136982

Chicago/Turabian Style

Pavasutthipaisit, Suvarin, Melanie Stoff, Tim Ebbecke, Malgorzata Ciurkiewicz, Sabine Mayer-Lambertz, Theresa Störk, Kevin D. Pavelko, Bernd Lepenies, and Andreas Beineke. 2021. "CARD9 Deficiency Increases Hippocampal Injury Following Acute Neurotropic Picornavirus Infection but Does Not Affect Pathogen Elimination" International Journal of Molecular Sciences 22, no. 13: 6982. https://doi.org/10.3390/ijms22136982

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