Molybdenum disulfide quantum dots (MoS2 QDs) represent an emerging class of two-dimensional (2D) atomically layered transition metal dichalcogenide nanostructures with few nanometers in lateral size, which show attractive potential as versatile platforms for theranostic applications in various neurological disorders. However, the potential impacts of MoS2 QDs on microglia remain unclear. In this report, we showed that exposure of microglia to MoS2 QDs triggered NLRP3 inflammasome activation as revealed by the cleavage of the inactive precursor of caspase-1 to its active form and the increased release of downstream pro-inflammatory cytokines, resulting in microglia cell death that occurred through caspase-1-dependent pyroptosis. We also found that MoS2 QDs activated autophagy, and suppression of autophagy by specific inhibitors potentiated MoS2 QD-induced pyroptosis. Additionally, MoS2 QDs stimulated mitochondria-derived reactive oxygen species (mtROS) generation in BV-2 cells. However, ROS scavengers could diminish the MoS2 QD-mediated NLRP3 inflammasome activation and pyroptotic cell death in microglia. Overall, our findings identified pyroptosis as a cellular response to MoS2 QD exposure in microglial cells, affording novel insights into the neurotoxicity of MoS2 QDs and facilitating the rational design and application of functional MoS2 QDs in neuroscience.
Keywords: MoS2 quantum dots; autophagy; microglia; neurotoxicity; pyroptosis.