nlrp3 inflammasome key mediator of neuroinflammation in murine japanese encephalitisnlrp3 inflammasome小鼠乙型脑炎的关键中介的存在.pdfVIP

NLRP3 Inflammasome: Key Mediator of Neuroinflammation in Murine Japanese Encephalitis Deepak Kumar Kaushik*., Malvika Gupta., Kanhaiya Lal Kumawat, Anirban Basu National Brain Research Centre, Manesar, Haryana, India Abstract Background: Japanese Encephalitis virus (JEV) is a common cause of acute and epidemic viral encephalitis. JEV infection is associated with microglial activation resulting in the production of pro-inflammatory cytokines including Interleukin-1 b (IL- 1b) and Interleukin-18 (IL-18). The Pattern Recognition Receptors (PRRs) and the underlying mechanism by which microglia identify the viral particle leading to the production of these cytokines is unknown. Methodology/Principal Findings: For our studies, we have used murine model of JEV infection as well as BV-2 mouse microglia cell line. In this study, we have identified a signalling pathway which leads to the activation of caspase-1 as the key enzyme responsible for the maturation of both IL-1b and IL-18 in NACHT, LRR and PYD domains-containing protein-3 (NLRP3) dependent manner. Depletion of NLRP3 results in the reduction of caspase-1 activity and subsequent production of these cytokines. Conclusion/Significance: Our results identify a mechanism mediated by Reactive Oxygen Species (ROS) production and potassium efflux as the two danger signals that link JEV infection to caspase-1 activation resulting in subsequent IL-1b and IL-18 maturation. Citation: Kaushik DK, Gupta M, Kumawat KL, Basu A (2012) NLRP3 Inflammasome: Key Mediator of Neuroinflammation in Murine Japanese Encephalitis. PLoS ONE 7(2): e32270. doi:10.1371/journal.pone.0032270 Editor: Tian Wang, University of Texas Medical Branch, United States of America Received November 1, 2011; Accepted January 24, 2012; Published February 29, 2012 Copyright: 2012 Kaushik et al. This is an o