| First Author | Jhan MK | Year | 2018 |
| Journal | J Leukoc Biol | Volume | 104 |
| Issue | 5 | Pages | 961-968 |
| PubMed ID | 30044892 | Mgi Jnum | J:266141 |
| Mgi Id | MGI:6203187 | Doi | 10.1002/JLB.MA1217-484R |
| Citation | Jhan MK, et al. (2018) Anti-TNF-alpha restricts dengue virus-induced neuropathy. J Leukoc Biol 104(5):961-968 |
| abstractText | Proinflammatory TNF-alpha facilitates dengue virus (DENV) infection in endovascular dysfunction and neurotoxicity. The introduction of TNF-alpha blocking therapy with Abs is performed to test its therapeutic effect in this study. In DENV-infected mice, TNF-alpha production in the brain accompanied the progression of neurotoxicity and encephalitis. DENV infection caused the loss of hippocampal neurons with TNF-alpha expression around damaged regions, and immunostaining showed the induction of apoptosis in hippocampal neurons. TNF-alpha was expressed in active microglia and astrocytes in DENV-infected mice. TNF-alpha 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-alpha transgenic mice represented the progressive disease development and administration of neutralizing TNF-alpha Ab reduced dengue encephalitis and mortality. These results demonstrate an immunopathogenesis of TNF-alpha for mediating DENV-induced encephalitis-associated neurotoxicity and that targeting TNF-alpha can be used as a strategy against dengue encephalitis. |
