Trichomonas vaginalis Induces NLRP3 Inflammasome Activation and Pyroptotic Cell Death in Human Macrophages.

Trichomonas vaginalis is a sexually transmitted, eukaryotic parasite that causes trichomoniasis, the most common nonviral, sexually transmitted disease in the USA and worldwide. Little is known about the molecular mechanisms involved in the host immune response to this widespread parasite. Here we report that T. vaginalis induces NLRP3 inflammasome activation in human macrophages, leading to caspase-1 activation and the processing of pro-IL-1ß to the mature and bioactive form of the cytokine. Using inhibitor-based approaches, we show that NLRP3 activation by T. vaginalis involves host cell detection of extracellular ATP via P2X7 receptors and potassium efflux. In addition, our data reveal that T. vaginalis inflammasome activation induces macrophage inflammatory cell death by pyroptosis, known to occur via caspase-1 cleavage of the gasdermin D protein, which assembles to form pores in the host cell membrane. We found that T. vaginalis-induced cytolysis of macrophages is attenuated in gasdermin D knockout cells. Lastly, in a murine challenge model, we detected IL-1ß production in vaginal fluids in response to T. vaginalis infection in vivo. Together, our findings mechanistically dissect how T. vaginalis contributes to the production of the proinflammatory IL-1ß cytokine and uncover pyroptosis as a mechanism by which the parasite can trigger host macrophage cell death.

Cardiovascular and autonomic response to environmental noise during sleep in night shift workers.

Polysomnograph, beat-by-beat heart rate and blood pressure were monitored in night shift workers exposed to environmental and laboratory noise events during day sleep. The study was carried out in a sleep laboratory. Subjects were nine young, healthy female night shift workers. Recorded noises from trucks, civilian aircraft, low altitude military aircraft and tones were presented at 55, 65, and 75 L(Amax). Sleep stage, heart rate, and systolic and diastolic blood pressures before and immediately after onset of noise events were compared. Spectral analyses of heart rate and blood pressure variabilities were used to compare sympathetic and parasympathetic nervous tone in 10-min. intervals containing noise and quiet. Heart rate was responsive to noise level but not noise type. Blood pressure increased primarily to sounds of sudden onset. Noise-induced awakening and alpha EEG responses were related to BP increase. Increase in HR was greatest when subjects were awakened by noise or already awake. Spectral analysis of BP variabilities indicated increased sympathetic vascular tone due to noise. Similar analyses of HR data indicated no noise effect. No habituation to noise was apparent over three consecutive sleep sessions. It was concluded that over the range of noise levels used, heart rate responds to noise level during sleep; blood pressure to sounds of sudden onset. Spectral analysis of blood pressure variabilities is a sensitive measure of autonomic nervous response to environmental noise and should also be studied in subjects sleeping at home.