The Involvement of Neuroinflammation in Dengue Viral Disease: Importance of Innate and Adaptive Immunity

Neuroinflammation (inflammation in brain) has been known to play an important role in the development of dengue virus disease. Recently, studies from both clinical and experimental models suggest the involvement of neuroinflammation in dengue viral disease. Studies in clinical setup demonstrated that, microglial cells are actively involved in the patients having dengue virus infection, showing involvement of innate immune response in neuroinflammation. It was further proved that, clinical isolates of dengue-2 virus were able to initiate the pathologic response when injected in the mice brain. Natural killer cells were also found to play a crucial role to activate adaptive immune response. Notably, CXCL10/IFN-inducible protein 10 and CXCR3 are involved in dengue virus-mediated pathogenesis and play an important role in the development of dengue virus-mediated paralysis. In a latest report, it was seen that intracranial injection of dengue virus increases the CD8+ T-cell infiltration in brain, showing an important mechanism of neuroinflammation during the dengue virus infection. A similar study has described that, when DENV-3 is injected into the mice, it enhances the infiltration of CD8+ and CD4+ T cells as well as neutrophils. Cells immune-reactive against NS3 antigen were found throughout the brain. In conclusion, we focus on the various molecular mechanisms which contribute to the basic understanding about the role of neuroinflammation in dengue fever. These mechanisms will help in better understanding dengue pathophysiology and thus help in the development of possible therapeutics.