TY - JOUR
T1 - Reframing sepsis immunobiology for translation
T2 - towards informative subtyping and targeted immunomodulatory therapies
AU - Shankar-Hari, Manu
AU - Calandra, Thierry
AU - Soares, Miguel P.
AU - Bauer, Michael
AU - Wiersinga, W. Joost
AU - Prescott, Hallie C.
AU - Knight, Julian C.
AU - Baillie, Kenneth J.
AU - Bos, Lieuwe D. J.
AU - Derde, Lennie P. G.
AU - Finfer, Simon
AU - Hotchkiss, Richard S.
AU - Marshall, John
AU - Openshaw, Peter J. M.
AU - Seymour, Christopher W.
AU - Venet, Fabienne
AU - Vincent, Jean-Louis
AU - le Tourneau, Christophe
AU - Maitland-van der Zee, Anke H.
AU - McInnes, Iain B.
AU - van der Poll, Tom
N1 - Publisher Copyright: © 2024 Elsevier Ltd
PY - 2024/4
Y1 - 2024/4
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85186178943&partnerID=8YFLogxK
U2 - 10.1016/S2213-2600(23)00468-X
DO - 10.1016/S2213-2600(23)00468-X
M3 - Review article
C2 - 38408467
SN - 2213-2600
VL - 12
SP - 323
EP - 336
JO - The Lancet Respiratory Medicine
JF - The Lancet Respiratory Medicine
IS - 4
ER -