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Bystander activated CD8+ T cells mediate neuropathology during viral infection via antigen-independent cytotoxicity

Author

Listed:
  • Elizabeth Balint

    (McMaster University)

  • Emily Feng

    (McMaster University)

  • Elizabeth C. Giles

    (McMaster University)

  • Tyrah M. Ritchie

    (McMaster University)

  • Alexander S. Qian

    (McMaster University, Hamilton Health Sciences)

  • Fatemeh Vahedi

    (McMaster University)

  • Amelia Montemarano

    (McMaster University)

  • Ana L. Portillo

    (McMaster University)

  • Jonathan K. Monteiro

    (McMaster University)

  • Bernardo L. Trigatti

    (McMaster University, Hamilton Health Sciences)

  • Ali A. Ashkar

    (McMaster University)

Abstract

Although many viral infections are linked to the development of neurological disorders, the mechanism governing virus-induced neuropathology remains poorly understood, particularly when the virus is not directly neuropathic. Using a mouse model of Zika virus (ZIKV) infection, we found that the severity of neurological disease did not correlate with brain ZIKV titers, but rather with infiltration of bystander activated NKG2D+CD8+ T cells. Antibody depletion of CD8 or blockade of NKG2D prevented ZIKV-associated paralysis, suggesting that CD8+ T cells induce neurological disease independent of TCR signaling. Furthermore, spleen and brain CD8+ T cells exhibited antigen-independent cytotoxicity that correlated with NKG2D expression. Finally, viral infection and inflammation in the brain was necessary but not sufficient to induce neurological damage. We demonstrate that CD8+ T cells mediate virus-induced neuropathology via antigen-independent, NKG2D-mediated cytotoxicity, which may serve as a therapeutic target for treatment of virus-induced neurological disease.

Suggested Citation

  • Elizabeth Balint & Emily Feng & Elizabeth C. Giles & Tyrah M. Ritchie & Alexander S. Qian & Fatemeh Vahedi & Amelia Montemarano & Ana L. Portillo & Jonathan K. Monteiro & Bernardo L. Trigatti & Ali A., 2024. "Bystander activated CD8+ T cells mediate neuropathology during viral infection via antigen-independent cytotoxicity," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-023-44667-0
    DOI: 10.1038/s41467-023-44667-0
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    References listed on IDEAS

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    1. Michael Dudek & Dominik Pfister & Sainitin Donakonda & Pamela Filpe & Annika Schneider & Melanie Laschinger & Daniel Hartmann & Norbert Hüser & Philippa Meiser & Felix Bayerl & Donato Inverso & Jennif, 2021. "Auto-aggressive CXCR6+ CD8 T cells cause liver immune pathology in NASH," Nature, Nature, vol. 592(7854), pages 444-449, April.
    2. Nilda Vanesa Ayala-Nunez & Gautier Follain & François Delalande & Aurélie Hirschler & Emma Partiot & Gillian L. Hale & Brigid C. Bollweg & Judith Roels & Maxime Chazal & Florian Bakoa & Margot Carocci, 2019. "Zika virus enhances monocyte adhesion and transmigration favoring viral dissemination to neural cells," Nature Communications, Nature, vol. 10(1), pages 1-16, December.
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