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

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Keywords

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

ASJC Scopus subject areas

  • Immunology
  • Cell Biology

Cite this

Jhan, M. K., Huangfu, W. C., Chen, Y. F., Kao, J. C., Tsai, T. T., Ho, M. R., Shen, T. J., Tseng, P. C., Wang, Y. T., & Lin, C. F. (Accepted/In press). Anti-TNF-α restricts dengue virus-induced neuropathy. Journal of Leukocyte Biology. https://doi.org/10.1002/JLB.MA1217-484R