Sepsis is life-threatening organ dysfunction caused by a dysregulated systemic inflammatory response to infection. Using unbiased single-cell transcriptional profiling, together with multidisciplinary collaborators, we discovered a new monocyte state – MS1 – that is significantly increased in both sepsis and severe COVID-19. The MS1 monocyte state can be induced by treatment of healthy bone marrow progenitors with plasma from patients with bacterial sepsis or severe COVID-19, suggesting that circulating factors present during sepsis or severe COVID-19 induce the development of MS1 cells in the bone marrow. In vitro, MS1 cells are broadly immunosuppressive and display reduced responses to stimulation, similar to myeloid-derived suppressor cells (MDSCs). Our current goals are to determine the mechanism by which MS1 cells contribute to immune dysregulation and systemic responses in sepsis and COVID-19.
