2025-05-09 イェール大学
<関連情報>
- https://news.yale.edu/2025/05/09/how-typhoid-fever-triggers-severe-neurological-symptoms
- https://www.nature.com/articles/s41564-025-02000-z
腸チフス毒素は血液脳関門を破壊して神経病理を引き起こす Typhoid toxin causes neuropathology by disrupting the blood–brain barrier
Heng Zhao,Jonatas Catarino,Gabrielle Stack,Ashley Kristant Albizu,Maria Lara-Tejero,Tamas L. Horvath & Jorge E. Galán
Nature Microbiology Published:08 May 2025
DOI:https://doi.org/10.1038/s41564-025-02000-z
Abstract
Typhoid fever, primarily caused by Salmonella Typhi, can result in severe life-threatening complications such as encephalopathy. Here we elucidate the mechanisms by which typhoid toxin, a unique virulence factor of S. Typhi, mediates the neuropathology associated with typhoid fever. Utilizing mice engineered to have specific tissues protected from toxin action and an in vitro model of the blood–brain barrier (BBB), we demonstrate that, rather than direct action on neuronal or glial cells, typhoid toxin causes neuropathology by disrupting the BBB. Intravenous tracer studies confirmed significant BBB permeability changes following toxin exposure, an effect we found to be mediated by typhoid toxin’s CdtB catalytic subunit. We demonstrate that corticosteroids are effective at mitigating BBB disruption in vivo, supporting their use for managing typhoid fever neurological complications. Our data reveal mechanistic insight into how typhoid toxin causes encephalopathy and suggest targeted therapeutic interventions to alleviate the severe neurological manifestations of typhoid fever.
