IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-023-44667-0.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-44667-0
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-023-44667-0?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    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.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Hao-Xian Zhu & Shu-Han Yang & Cai-Yue Gao & Zhen-Hua Bian & Xiao-Min Chen & Rong-Rong Huang & Qian-Li Meng & Xin Li & Haosheng Jin & Koichi Tsuneyama & Ying Han & Liang Li & Zhi-Bin Zhao & M. Eric Ger, 2024. "Targeting pathogenic CD8+ tissue-resident T cells with chimeric antigen receptor therapy in murine autoimmune cholangitis," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    2. Caihua Zhang & Kang Li & Hongzhang Zhu & Maosheng Cheng & Shuang Chen & Rongsong Ling & Cheng Wang & Demeng Chen, 2024. "ITGB6 modulates resistance to anti-CD276 therapy in head and neck cancer by promoting PF4+ macrophage infiltration," Nature Communications, Nature, vol. 15(1), pages 1-23, December.
    3. Paul Little & Si Liu & Vasyl Zhabotynsky & Yun Li & Dan-Yu Lin & Wei Sun, 2023. "A computational method for cell type-specific expression quantitative trait loci mapping using bulk RNA-seq data," Nature Communications, Nature, vol. 14(1), pages 1-13, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-023-44667-0. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.