Sepsis pathogenesis and outcome are shaped by the balance between the transcriptional states of systemic inflammation and antimicrobial response

Rachel Brandes-Leibovitz, Anca Riza, Gal Yankovitz, Andrei Pirvu, Stefania Dorobantu, Adina Dragos, Ioana Streata, Isis Ricaño-Ponce, Aline de Nooijer, Florentina Dumitrescu, Nikolaos Antonakos, Eleni Antoniadou, George Dimopoulos, Ioannis Koutsodimitropoulos, Theano Kontopoulou, Dimitra Markopoulou, Eleni Aimoniotou, Apostolos Komnos, George N. Dalekos, Mihai IoanaEvangelos J. Giamarellos-Bourboulis, Irit Gat-Viks*, Mihai G. Netea*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

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 with high SI, patients with low R, or both. We show how this R/SI framework can be used to guide patient stratification that is relevant to disease prognosis and management, outperforming existing classifications of sepsis.

Original languageEnglish
Article number101829
JournalCell Reports Medicine
Volume5
Issue number11
DOIs
StatePublished - 19 Nov 2024

Keywords

  • immune response
  • immunotheraphy
  • infection
  • patient stratification
  • personalized medicine
  • precision medicine
  • sepsis
  • septic shock
  • systemic inflammation

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