Bystander activated CD8+ T cells mediate neuropathology during viral infection via antigen-independent cytotoxicity, 2024, Ashkar et al

Bystander activated CD8+ T cells mediate neuropathology during viral infection via antigen-independent cytotoxicity
Nature, open access: https://www.nature.com/articles/s41467-023-44667-0

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.

 

Bizarrely, I saw this study promoted in many places, framed this way by McMaster university it seems, as if "busting the myth" that viruses cause neurological disease, because rather it's the immune system's response. Which is really a bizarre potato-potahto since there is no infectious disease without an immune response.

 

Summary quotes from the discussion —