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Anti‐TNF‐α restricts dengue virus‐induced neuropathy
Author(s) -
Jhan MingKai,
HuangFu WeiChun,
Chen YiFan,
Kao JoChi,
Tsai TsungTing,
Ho MinRu,
Shen TingJing,
Tseng PoChun,
Wang YungTing,
Lin ChiouFeng
Publication year - 2018
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.ma1217-484r
Subject(s) - biology , dengue virus , virology , dengue fever , virus , tumor necrosis factor alpha , immunology , flavivirus
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.