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- Title
Anti‐TNF‐α restricts dengue virus‐induced neuropathy.
- Authors
Jhan, Ming‐Kai; Kao, Jo‐Chi; Tsai, Tsung‐Ting; Ho, Min‐Ru; Shen, Ting‐Jing; Tseng, Po‐Chun; Wang, Yung‐Ting; Lin, Chiou‐Feng; HuangFu, Wei‐Chun; Chen, Yi‐Fan
- Abstract
Proinflammatory TNF‐α facilitates dengue virus (DENV) infection in endovascular dysfunction and neurotoxicity. The introduction of TNF‐α blocking therapy with Abs is performed to test its therapeutic effect in this study. In DENV‐infected mice, TNF‐α production in the brain accompanied the progression of neurotoxicity and encephalitis. DENV infection caused the loss of hippocampal neurons with TNF‐α expression around damaged regions, and immunostaining showed the induction of apoptosis in hippocampal neurons. TNF‐α was expressed in active microglia and astrocytes in DENV‐infected mice. TNF‐α facilitated DENV‐induced neurotoxicity in vitro in murine Neuro‐2a cells. Using a currently established encephalitic mouse model in which DENV infection causes progressive hunchback posture, limbic seizures, limbic weakness, paralysis, and lethality 7 days postinfection, we showed that TNF‐α transgenic mice represented the progressive disease development and administration of neutralizing TNF‐α Ab reduced dengue encephalitis and mortality. These results demonstrate an immunopathogenesis of TNF‐α for mediating DENV‐induced encephalitis‐associated neurotoxicity and that targeting TNF‐α can be used as a strategy against dengue encephalitis. Dengue virus infection induces TNF‐α expression around the damaged neuronal cells in the brain while TNF‐α blockade ameliorates dengue neurotoxicity and encephalitis.
- Subjects
TUMOR necrosis factors; DENGUE viruses; NEUROPATHY; ENCEPHALITIS; NEUROTOXICOLOGY
- Publication
Journal of Leukocyte Biology, 2018, Vol 104, Issue 5, p961
- ISSN
0741-5400
- Publication type
Article
- DOI
10.1002/JLB.MA1217-484R