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.

Original languageEnglish
JournalJournal of Leukocyte Biology
DOIs
Publication statusAccepted/In press - Jan 1 2018

Fingerprint

Dengue Virus
Encephalitis
Virus Diseases
Dengue
Neurons
Microglia
Therapeutic Uses
Posture
Astrocytes
Paralysis
Transgenic Mice
Seizures
Apoptosis
Mortality
Brain

Keywords

  • Dengue virus
  • Encephalitis
  • Infection
  • Mice
  • Neurotoxicity
  • TNF-α

ASJC Scopus subject areas

  • Immunology
  • Cell Biology

Cite this

Anti-TNF-α restricts dengue virus-induced neuropathy. / Jhan, Ming Kai; Huangfu, Wei Chun; Chen, Yi Fan; Kao, Jo Chi; Tsai, Tsung Ting; Ho, Min Ru; Shen, Ting Jing; Tseng, Po Chun; Wang, Yung Ting; Lin, Chiou Feng.

In: Journal of Leukocyte Biology, 01.01.2018.

Research output: Contribution to journalArticle

Jhan, Ming Kai ; Huangfu, Wei Chun ; Chen, Yi Fan ; Kao, Jo Chi ; Tsai, Tsung Ting ; Ho, Min Ru ; Shen, Ting Jing ; Tseng, Po Chun ; Wang, Yung Ting ; Lin, Chiou Feng. / Anti-TNF-α restricts dengue virus-induced neuropathy. In: Journal of Leukocyte Biology. 2018.
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