NLRP3 inflammasomes modulate sleep responses to S. pneumoniae in mice 2253065

Abstract Introduction S. pneumoniae is a common bacterial infection in humans that induces inflammation in the lung and brain affecting sleep and electroencephalogram (EEG) slow-wave-activity (SWA). S. pneumoniae infections can potentially be fatal and cause meningitis especially in vulnerable population such as young children, older adults, and individuals with compromised immune systems. NLRP3 inflammasomes are critical regulators of homeostatic sleep and SWA responses to toxin challenge. Consequently, we aimed to investigate if NLRP3 inflammasomes are involved in sleep and SWA to S. pneumoniae in mice lacking NLRP3. Methods NLRP3 knockout (KO) mice and wild-type (WT) controls were implanted with electrodes for polysomnography (PSG) recordings. Baseline sleep was recorded for 24 H. Thereafter, mice were infected intranasally with S. pneumoniae, and PSG was recorded for 3 days. Results Baseline sleep and SWA were not significantly reduced in NLRP3 KO mice compared to WT mice. WT mice had increased non-rapid-eye movement sleep (NREMS) and SWA responses within the first 24 H post-infection that continued to increase for the next 2 days compared to baseline values. NLRP3 KO mice exhibited enhancements in NREMS and SWA after infection, although these changes were smaller and delayed when compared to WT mice. Conclusion These data suggest that NLRP3 inflammasomes are involved in the progression of sleep and SWA responses to S. pneumoniae. Funding Source Department of Veteran Affairs I01BX005379 (MRZ) and I21RX003722 (MRZ) Topic Categories Neuroimmunology (NEUR)