| Popis: |
Different immune phenotypes characterize sepsis patients, including hyperinflammation and/or immunosuppression, but the biological mechanisms driving this heterogeneity remain largely unknown. We used single-cell RNA sequencing to profile circulating leukocytes of healthy controls and sepsis patients classified as eitherhyperinflammatory(macrophage activation-like syndrome [MALS]),immune paralysis, orunclassified(when criteria for neither of these two immune subgroups were applicable). Pronounced differences were detected in the transcriptional signature of monocytes from sepsis patients, with clear distinction between MALS and immune paralysis patients. Unsupervised clustering analysis revealed the existence of MALS-specific monocyte clusters, as well as one sepsis-specific monocyte cluster that was linked to disease severity. In separate cohorts, urosepsis was characterized by heterogeneous MALS and immunosuppression monocyte signatures, while MALS-specific monocyte clusters showed overlapping transcriptional signatures with severe COVID-19. In conclusion, our findings shed light on the heterogeneous immune landscape underlying sepsis, and provide opportunities for patient stratification for future therapeutic development. |
