Tumor necrosis factor receptor-associated death domain mediated neuronal death contributes to the glial activation and subsequent neuroinflammation in Japanese encephalitis.
While a number of studies have documented the importance of microglia in central nervous system (CNS) response to injury, infection and in disease state, little is known regarding how the neuronal death initiates the cascades of secondary neuroinflammation. We have exploited an experimental model of Japanese encephalitis to better understand how neuronal death following viral infection initiates microglial activation following Japanese encephalitis virus infection. We have earlier shown that the altered expression of tumor necrosis factor receptor-1 (TNFR-1) and TNFR associated death domain (TRADD) following Japanese encephalitis virus infection regulates the downstream apoptotic cascades. Here we have reported that silencing TRADD expression with small-interfering RNA reduced neuronal apoptosis and subsequent microglial and astroglial activation and release of various pro-inflammatory mediators. Our findings suggest that the engagement of TNFR-1 and TRADD following Japanese encephalitis virus infection plays a crucial role in glial activation also and influences the outcome of viral pathogenesis.
Swarup
Vivek
V
National Brain Research Centre, Manesar, Haryana, India.
Ghosh
Joydeep
J
Das
Sulagna
S
Basu
Anirban
A
D000818:Animals; D001253:Astrocytes / Q000187:drug effects; D015153:Blotting, Western; D016923:Cell Death / Q000235:genetics; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000096:biosynthesis / Q000235:genetics; D016207:Cytokines / Q000737:chemistry / Q000378:metabolism; D004672:Encephalitis, Japanese / Q000473:pathology*; D005260:Female; D007150:Immunohistochemistry; D007249:Inflammation / Q000473:pathology*; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D007962:Leukocytes / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D017628:Microglia / Q000502:physiology*; D009474:Neurons / Q000473:pathology* / Q000502:physiology*; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis / Q000235:genetics; D034741:RNA, Small Interfering / Q000494:pharmacology; D019707:Receptors, Chemokine / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053199:TNF Receptor-Associated Death Domain Protein / Q000235:genetics / Q000502:physiology*; D013778:Tetrazolium Salts; D013844:Thiazoles; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis; D019562:Viral Load
D016207:Cytokines; D034741:RNA, Small Interfering; D019707:Receptors, Chemokine; D053199:TNF Receptor-Associated Death Domain Protein; D013778:Tetrazolium Salts; D013844:Thiazoles; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; C022616:thiazolyl blue