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 McInnes; Tom van der Poll

doi:10.1016/S2213-2600(23)00468-X

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

Lancet Respir Med. 2024 Apr;12(4):323-336. doi: 10.1016/S2213-2600(23)00468-X. Epub 2024 Feb 23.

Authors

Manu Shankar-Hari¹, Thierry Calandra², Miguel P Soares³, Michael Bauer⁴, W Joost Wiersinga⁵, Hallie C Prescott⁶, Julian C Knight⁷, Kenneth J Baillie⁸, Lieuwe D J Bos⁹, Lennie P G Derde¹⁰, Simon Finfer¹¹, Richard S Hotchkiss¹², John Marshall¹³, Peter J M Openshaw¹⁴, Christopher W Seymour¹⁵, Fabienne Venet¹⁶, Jean-Louis Vincent¹⁷, Christophe Le Tourneau¹⁸, Anke H Maitland-van der Zee¹⁹, Iain B McInnes²⁰, Tom van der Poll⁵

Affiliations

¹ Institute for Regeneration and Repair, College of Medicine and Veterinary Medicine, The University of Edinburgh, Edinburgh, UK. Electronic address: [email protected].
² Service of Immunology and Allergy, Center of Human Immunology Lausanne, Department of Medicine and Department of Laboratory Medicine and Pathology, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland.
³ Instituto Gulbenkian de Ciência, Oeiras, Portugal.
⁴ Center for Sepsis Control and Care, Jena University Hospital, Jena, Germany.
⁵ Center for Experimental and Molecular Medicine and Division of Infectious Diseases, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands.
⁶ Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
⁷ Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
⁸ Institute for Regeneration and Repair, College of Medicine and Veterinary Medicine, The University of Edinburgh, Edinburgh, UK.
⁹ Department of Intensive Care, Academic Medical Center, Amsterdam, Netherlands.
¹⁰ Intensive Care Center, University Medical Center Utrecht, Utrecht, Netherlands.
¹¹ Critical Care Division, The George Institute for Global Health, University of New South Wales, Sydney, NSW, Australia.
¹² Department of Anesthesiology and Critical Care Medicine, Washington University School of Medicine in St Louis, St Louis, MO, USA.
¹³ Interdepartmental Division of Critical Care, University of Toronto, Toronto, ON, Canada.
¹⁴ National Heart and Lung Institute, Imperial College London, London, UK.
¹⁵ Department of Critical Care Medicine, The Clinical Research, Investigation, and Systems Modeling of Acute illness (CRISMA) Center, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
¹⁶ Immunology Laboratory, Edouard Herriot Hospital, Hospices Civils de Lyon, Lyon, France.
¹⁷ Department of Intensive Care, Hôpital Erasme, Brussels, Belgium.
¹⁸ Department of Drug Development and Innovation (D3i), Institut Curie, Paris-Saclay University, Paris, France.
¹⁹ Department of Pulmonary Medicine, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands.
²⁰ College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.

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.

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

Authors

Affiliations

Abstract

Publication types

MeSH terms

Grants and funding