Persistent NLRP3 inflammasome activation is associated with delayed immunosuppression in septic patients

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Coudereau, R. | Bodinier, M. | Lukaszewicz, A. C. | B, F. Py | Argaud, L. | Cour, M. | Bidar, F. | Cerrato, E. | Garnier, L. | Gossez, M. | Venet, F. | Monneret, G.

Edité par CCSD ; Society for Leukocyte Biology -

International audience. Sepsis triggers a complex response marked by the simultaneous presence of pro-inflammatory and immunosuppressive elements, disrupting the mechanisms intended to maintain homeostasis. While the NLRP3 inflammasome has been demonstrated to contribute to the inflammatory side, its connection with delayed sepsis-induced immunosuppression remains unexplored. The present objective was to concomitantly and prospectively assess NLRP3 activation (IL-1β, IL-18 and soluble receptors) and features of immune failure (IL-10, mHLA-DR, MDSC) in septic patients. To validate our findings, we conducted a transcriptomic analysis of mRNA of NLRP3 related genes (IL-18R1, IL-1R2) on an additional cohort of 107 patients. Two distinct endotypes of endotypes were identified. One cluster displayed moderate inflammation rapidly returning to normal values, while the other exhibited a higher inflammatory response persisting until day 28 which was associated with persistent marked immunosuppression and higher 28-day mortality. Identifying endotypes with different pro-/anti-inflammatory trajectories could hold important clinical implications for the management of sepsis.

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