Correction: Identification of Biomarkers of Response to IFNg during Endotoxin Tolerance: Application to Septic Shock

Allantaz-Frager, Florence; Turrel-Davin, Fanny; Venet, Fabienne; Monnin, CÃ©cile; Jean, AmÃ©lie De Saint; Barbalat, VÃ©ronique; Cerrato, Elisabeth; Pachot, Alexandre; Lepape, Alain; Monneret, Guillaume

doi:10.1371/annotation/5cdfb251-b4ab-4346-b64d-589a3344ef78

Cited by 5 publications

(1 citation statement)

References 35 publications

(56 reference statements)

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“…Alternatively, pyroptosis could be the main actor, releasing cytokines but leaving cells unable to respond to additional challenges [25,26]. These results bring to mind the phenomenon of endotoxin tolerance [13,27], which is well-established in sepsis.…”

Section: Discussionmentioning

confidence: 96%

Altered Ex Vivo NLRP3 Inflammasome Activation Is Associated with 28-Day Mortality in Septic Patients

Coudereau,

Monneret,

Lukaszewicz

et al. 2023

Viruses

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Sepsis is a life-threatening organ dysfunction caused by a dysregulated response to infection. In this context, the aberrant activation of the NLRP3 inflammasome has been documented mostly through the measurement of increased plasmatic concentrations of IL-1β and IL-18. At the cellular level, contradictory results have been published. However, no study has comprehensively monitored NLRP3 inflammasome activation at the basal level and after ex vivo reactivation of whole blood monocytes and neutrophils focusing on ICU patients with bacterial and viral sepsis, including a longitudinal analysis. Thus, we conducted a prospective longitudinal study, examining NLRP3 inflammasome functionality in COVID-19 ICU patients (n = 15) and bacterial septic shock patients (n = 17) during the first week of ICU hospitalization, compared with healthy donors. Using two whole-blood flow cytometry assays, we detected ASC speck-positive monocytes (i.e., monocytes presenting the polymerization of ASC proteins) and activated caspase-1 in polymorphonuclear cells as read-outs, both at baseline and following nigericin stimulation, a drug that forms pores and activates the NLRP3 inflammasome. Our findings showed that, at baseline and regardless of the type of infection, patients exhibited reduced ASC speck-positive monocytes and decreased activated caspase-1 in PMN compared to healthy volunteers. This decrease was prominent at day 0. Following nigericin stimulation, this reduction was also observed and persisted throughout the first week of hospitalization, irrespective of the cellular population or parameter being considered. Notably, at day 0, this diminished activation and response to stimulation of NLRP3 was associated with a higher 28-day mortality rate. Consequently, our observations highlighted a concurrent decline in both basal expression and ex vivo activation of the NLRP3 inflammasome in circulating myeloid cells from patients with bacterial and viral sepsis in association with increased mortality.

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