Anti-TNF-α restricts dengue virus-induced neuropathy

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

article

Ming-Kai Jhan¹  Wei-Chun HuangFu³  Yi-Fan Chen⁵  Jo-Chi Kao¹  Tsung-Ting Tsai¹  Min-Ru Ho¹  Ting-Jing Shen¹  Po-Chun Tseng¹  Yung-Ting Wang¹  Chiou-Feng Lin¹ 

[1] Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University;Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University;The Ph.D. Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University;Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University;The Ph.D. Program for Translational Medicine, College of Medical Science and Technology, Taipei Medical University

关键词: dengue virus;    encephalitis;    infection;    mice;    neurotoxicity;    TNF-α;   

DOI  :  10.1002/JLB.MA1217-484R

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Proinflammatory TNF-? facilitates dengue virus (DENV) infection in endovascular dysfunction and neurotoxicity. The introduction of TNF-? blocking therapy with Abs is performed to test its therapeutic effect in this study. In DENV-infected mice, TNF-? production in the brain accompanied the progression of neurotoxicity and encephalitis. DENV infection caused the loss of hippocampal neurons with TNF-? expression around damaged regions, and immunostaining showed the induction of apoptosis in hippocampal neurons. TNF-? was expressed in active microglia and astrocytes in DENV-infected mice. TNF-? 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-? transgenic mice represented the progressive disease development and administration of neutralizing TNF-? Ab reduced dengue encephalitis and mortality. These results demonstrate an immunopathogenesis of TNF-? for mediating DENVinduced encephalitis-associated neurotoxicity and that targeting TNF-? can be used as a strategy against dengue encephalitis.

【 授权许可】

CC BY