Reframing sepsis immunobiology for translation: towards informative subtyping and targeted immunomodulatory therapies

Manu Shankar-Hari, Thierry Calandra, Miguel P. Soares, Michael Bauer, W. Joost Wiersinga, Hallie C. Prescott, Julian C. Knight, Kenneth J. Baillie, Lieuwe D.J. Bos, Lennie P.G. Derde, Simon Finfer, Richard S. Hotchkiss, John Marshall, Peter J.M. Openshaw, Christopher W. Seymour, Fabienne Venet, Jean Louis Vincent, Christophe Le Tourneau, Anke H. Maitland-van der Zee, Iain B. McInnesTom van der Poll

Research output: Contribution to journalReview articlepeer-review

13 Scopus citations

Abstract

Sepsis is a common and deadly condition. Within the current model of sepsis immunobiology, the framing of dysregulated host immune responses into proinflammatory and immunosuppressive responses for the testing of novel treatments has not resulted in successful immunomodulatory therapies. Thus, the recent focus has been to parse observable heterogeneity into subtypes of sepsis to enable personalised immunomodulation. In this Personal View, we highlight that many fundamental immunological concepts such as resistance, disease tolerance, resilience, resolution, and repair are not incorporated into the current sepsis immunobiology model. The focus for addressing heterogeneity in sepsis should be broadened beyond subtyping to encompass the identification of deterministic molecular networks or dominant mechanisms. We explicitly reframe the dysregulated host immune responses in sepsis as altered homoeostasis with pathological disruption of immune-driven resistance, disease tolerance, resilience, and resolution mechanisms. Our proposal highlights opportunities to identify novel treatment targets and could enable successful immunomodulation in the future.

Original languageEnglish
Pages (from-to)323-336
Number of pages14
JournalThe Lancet Respiratory Medicine
Volume12
Issue number4
DOIs
StatePublished - Apr 2024

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