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bioRxiv · 10.1101/2022.02.03.479081

Circulatory exosomes from COVID-19 patients trigger NLRP3 inflammasome in endothelial cells

Sur, S.·steele, r.·Isbell, S.·Ray, R.·Ray, R. B.
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Abstract

SARS-CoV-2 infection induces inflammatory response, cytokine storm, venous thromboembolism, coagulopathy, and multiple organ damage. Resting endothelial cells prevent coagulation, control blood flow and inhibit inflammation. However, it remains unknown how SARS-CoV-2 induces strong molecular signals in distant cells for immunopathogenesis. In this study, we examined the consequence of human endothelial cells (microvascular endothelial cells (HMEC-1) and liver endothelial cells (TMNK-1)) to exosomes from plasma of severe COVID-19 patients. We observed a significant induction of NLRP3, caspase-1 and IL-1{beta} mRNA expression in the endothelial cells following exposure to exosomes from plasma of COVID-19 patients as compared to that of healthy donors. Activation of caspase-1 was noted in the endothelial cell culture medium following exposure to the COVID-19 exosomes. Further, COVID-19 exosomes significantly induced mature IL-1{beta} secretion in the endothelial cell culture medium. Thus, our results demonstrated for the first time that exosomes from COVID-19 plasma trigger NLRP3 inflammasome in endothelial cells of distant organs.

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Sur, S., steele, r., Isbell, S., Ray, R., Ray, R. B.. 2022-02-04. Circulatory exosomes from COVID-19 patients trigger NLRP3 inflammasome in endothelial cells. https://doi.org/10.1101/2022.02.03.479081

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