biostudies-literatureBrandes-Leibovitz REuropean Research CouncilHorizon 2020 Framework Programme101829https://www.ebi.ac.uk/biostudies/studies/S-EPMC11604535biostudies-literatureUnknown5(11)Patients with sepsis differ in their clinical presentations and immune dysregulation in response to infection, but the fundamental processes that determine this heterogeneity remain elusive. Here, we aim to understand which types of immune dysregulation characterize patients with sepsis. To that end, we investigate sepsis pathogenesis in the context of two transcriptional states: one represents the immune response to eliminate pathogens (resistance, R) and the other is associated with systemic inflammation (SI). We find that patients with sepsis share a molecular fingerprint of a low R-to-SI balance-i.e., a low R relative to the level of SI. Differences between patients with sepsis are explained by the wide diversity of R and SI states that fall under this fingerprint, such as patients witCell reports. MedicineSepsis pathogenesis and outcome are shaped by the balance between the transcriptional states of systemic inflammation and antimicrobial response.PMC11604535637885833247Ioana MYankovitz GPirvu AKomnos ADragos ADalekos GNStreata IDumitrescu FRicano-Ponce IKoutsodimitropoulos IGiamarellos-Bourboulis EJAntoniadou EGat-Viks Ide Nooijer AMarkopoulou DRiza AAntonakos NKontopoulou TDimopoulos GBrandes-Leibovitz RDorobantu SAimoniotou ENetea MGfalseSepsis pathogenesis and outcome are shaped by the balance between the transcriptional states of systemic inflammation and antimicrobial response.Patients with sepsis differ in their clinical presentations and immune dysregulation in response to infection, but the fundamental processes that determine this heterogeneity remain elusive. Here, we aim to understand which types of immune dysregulation characterize patients with sepsis. To that end, we investigate sepsis pathogenesis in the context of two transcriptional states: one represents the immune response to eliminate pathogens (resistance, R) and the other is associated with systemic inflammation (SI). We find that patients with sepsis share a molecular fingerprint of a low R-to-SI balance-i.e., a low R relative to the level of SI. Differences between patients with sepsis are explained by the wide diversity of R and SI states that fall under this fingerprint, such as patients wit2024-01-01T00:00:00Z2024 Nov2026-06-03T01:04:38.153Z2025-04-04T01:58:24.775ZS-EPMC116045353956646810.1016/j.xcrm.2024.101829