Rabies virus induces expression of tlr-3 and its associated cytokines in swiss-albino mice
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The present study was conducted with an aim to investigate involvement of TLR-3 and its associated cytokines (IL1-α, TNF-α, and IFN-α) in the pathogenesis of rabies. A total of 80 adult Swiss albino mice consisting of 20 mice in four groups viz., Challenge Virus Standard (CVS) strain of rabies (GI), poly IC as TLR-3 agonist with CVS (GPI), poly IC (GP) and PBS (GC) as controls were taken. Clinical history score revealed less severe and delayed onset of clinical signs in GPI group. This resulted in better survival of mice on different time points in GPI than in GI. The non-suppurative meningo-encephalitis characterized by perivascular cuffing, focal to diffuse gliosis and neuronal damage (necrosis/ apoptosis) scored less in GPI than in GI. These lesions progressed with time and were more severe on day 8th onwards. The hippocampus, particularly CA1 and CA2 regions, had more severe lesions followed by cerebral hemisphere and the thalamus. The positive apoptotic signals on 12th DPI in GI but not in GPI were supported by the increased expression of caspase 1 in GI on 12th DPI. The TLR-3 and its associated cytokines showed higher expression in GPI than in GI. Further, the presence of virus in brain was detected by both conventional and Real Time PCR using N gene specific primers (533 bp) as early as on 2nd DPI in both the infected groups. The study suggests that TLR-3 induction by its ligand poly IC has some role in reducing the development of disease, through pro-inflammatory cytokines. Further studies are needed to explore the possibility of TLR-3 for therapeutic purposes in rabies and other related diseases.