Reframing Sepsis Immunobiology for Translation

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

Reframing Sepsis Immunobiology for Translation

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

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract / Description of output

Sepsis is a common and deadly condition. The current framing of dysregulated host immune responses within the sepsis immunobiology model into pro-inflammatory and immunosuppressive responses for testing novel treatments, have not resulted in successful immunomodulatory therapies. Thus, the recent focus has been to parse observable heterogeneity into subtypes of sepsis to enable personalized immunomodulation. In this perspective 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 broaden beyond subtyping, onto identifying deterministic molecular
networks or dominant mechanisms. We explicitly reframe the dysregulated host immune responses in sepsis as pathologic disruption and/or alteration in homeostasis of the immune-driven resistance, tolerance and resolution mechanisms occurring concurrently. Our reframing highlights novel treatment opportunities and could enable successful immunomodulation in the future.
Keywords: Sepsis, immunobiology, precision medicine, molecular mechanisms, subtyping, immunomodulation

Original language	English
Journal	The Lancet Respiratory Medicine
Publication status	Published - 23 Feb 2024

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Shankar-Hari, M., Calandra, T., Soares, M. P., Bauer, M., Wiersinga, W. J., Prescott, H. C., Knight, J. C., Baillie, J. K., Bos, L. D. J., Derde, L. P. G., Finfer, S., Hotchkiss, R. S., Marshall, J., Openshaw, P., Seymour, C. W., Venet, F., Vincent, J.-L., Le Tourneau, C., Maitland-van der Zee, A.-H., ... Poll, T. V. D. (2024). Reframing Sepsis Immunobiology for Translation. The Lancet Respiratory Medicine.

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title = "Reframing Sepsis Immunobiology for Translation",

abstract = "Sepsis is a common and deadly condition. The current framing of dysregulated host immune responses within the sepsis immunobiology model into pro-inflammatory and immunosuppressive responses for testing novel treatments, have not resulted in successful immunomodulatory therapies. Thus, the recent focus has been to parse observable heterogeneity into subtypes of sepsis to enable personalized immunomodulation. In this perspective 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 broaden beyond subtyping, onto identifying deterministic molecularnetworks or dominant mechanisms. We explicitly reframe the dysregulated host immune responses in sepsis as pathologic disruption and/or alteration in homeostasis of the immune-driven resistance, tolerance and resolution mechanisms occurring concurrently. Our reframing highlights novel treatment opportunities and could enable successful immunomodulation in the future.Keywords: Sepsis, immunobiology, precision medicine, molecular mechanisms, subtyping, immunomodulation",

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

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month = feb,

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language = "English",

journal = "The Lancet Respiratory Medicine",

issn = "2213-2600",

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Shankar-Hari, M, Calandra, T, Soares, MP, Bauer, M, Wiersinga, WJ, Prescott, HC, Knight, JC, Baillie, JK, Bos, LDJ, Derde, LPG, Finfer, S, Hotchkiss, RS, Marshall, J, Openshaw, P, Seymour, CW, Venet, F, Vincent, J-L, Le Tourneau, C, Maitland-van der Zee, A-H, McInnes, IB & Poll, TVD 2024, 'Reframing Sepsis Immunobiology for Translation', The Lancet Respiratory Medicine.

TY - JOUR

T1 - Reframing Sepsis Immunobiology for Translation

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, J Kenneth

AU - Bos, Lieuwe D J

AU - Derde, Lennie P G

AU - Finfer, Simon

AU - Hotchkiss, Richard S.

AU - Marshall, John

AU - Openshaw, Peter

AU - Seymour, Christopher W

AU - Venet, Fabienne

AU - Vincent, Jean-Louis

AU - Le Tourneau, Christophe

AU - Maitland-van der Zee, Anke-Hilse

AU - McInnes, Iain B.

AU - Poll, Tom van der

PY - 2024/2/23

Y1 - 2024/2/23

N2 - Sepsis is a common and deadly condition. The current framing of dysregulated host immune responses within the sepsis immunobiology model into pro-inflammatory and immunosuppressive responses for testing novel treatments, have not resulted in successful immunomodulatory therapies. Thus, the recent focus has been to parse observable heterogeneity into subtypes of sepsis to enable personalized immunomodulation. In this perspective 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 broaden beyond subtyping, onto identifying deterministic molecularnetworks or dominant mechanisms. We explicitly reframe the dysregulated host immune responses in sepsis as pathologic disruption and/or alteration in homeostasis of the immune-driven resistance, tolerance and resolution mechanisms occurring concurrently. Our reframing highlights novel treatment opportunities and could enable successful immunomodulation in the future.Keywords: Sepsis, immunobiology, precision medicine, molecular mechanisms, subtyping, immunomodulation

AB - Sepsis is a common and deadly condition. The current framing of dysregulated host immune responses within the sepsis immunobiology model into pro-inflammatory and immunosuppressive responses for testing novel treatments, have not resulted in successful immunomodulatory therapies. Thus, the recent focus has been to parse observable heterogeneity into subtypes of sepsis to enable personalized immunomodulation. In this perspective 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 broaden beyond subtyping, onto identifying deterministic molecularnetworks or dominant mechanisms. We explicitly reframe the dysregulated host immune responses in sepsis as pathologic disruption and/or alteration in homeostasis of the immune-driven resistance, tolerance and resolution mechanisms occurring concurrently. Our reframing highlights novel treatment opportunities and could enable successful immunomodulation in the future.Keywords: Sepsis, immunobiology, precision medicine, molecular mechanisms, subtyping, immunomodulation

M3 - Article

SN - 2213-2600

JO - The Lancet Respiratory Medicine

JF - The Lancet Respiratory Medicine

ER -

Reframing Sepsis Immunobiology for Translation

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