A burns and COVID-19 shared stress responding gene network deciphers CD1C-CD141-DCs as the key cellular components in septic prognosis

Abstract

AbstractDifferential body responses to various stresses, infectious or noninfectious, govern clinical outcomes ranging from asymptoma to death. However, the common molecular and cellular nature of the stress responsome across different stimuli is not described. In this study, we compared the expression behaviors between burns and COVID-19 infection by choosing the transcriptome of peripheral blood from related patients as the analytic target since the blood cells reflect the systemic landscape of immune homeostasis. We identified an immune co-stimulator (CD86)-centered network, named stress-response core (SRC), which coordinated multiple immune processes and was robust in membership and highly related to the clinical traits in both burns and COVID-19. An independent whole blood single-cell RNA sequencing of COVID-19 patients demonstrated that the monocyte-dendritic cell (Mono-DC) wing was the major cellular source of the SRC, among which the higher expression of the SRC in the monocyte was associated with the asymptomatic COVID-19 patients, while the quantity-restricted and function-defected CD1C-CD141-DCs were recognized as the key signature which linked to bad consequences in COVID-19. Specifically, the proportion of the CD1C-CD141-DCs and their SRC expression levels were step-wise reduced along with worse clinic conditions while the sub-cluster of CD1C-CD141-DCs of the critical COVID-19 patients was characterized of IFN signaling quiescence, high mitochondrial metabolism and immune-communication inactivation. Thus, our study identified an expression-synchronized and function-focused gene network which was decreased under burns and COVID-19 stress and argued the CD1C-CD141-DC as the prognosis-related cell population which might serve as a new target of diagnosis and therapy.