Sepsis is a life-threatening organ dysfunction caused by the host's dysregulated immune response to infection. It represents a major global public health challenge. A state of post-septic compensatory immunosuppression may contribute to excess mortality by promoting secondary infections, thereby prolonging the stay in the intensive care unit and increasing the risk of death.
New therapeutic strategies to complement antimicrobial treatments-which may correct sepsis-induced functional alterations in immune cells (such as endotoxin tolerance and reduced HLA-DR expression), partly mediated by metabolic abnormalities-are currently being investigated. Among these, mesenchymal stromal cells (MSCs) appear particularly promising. They are capable of reprogramming immune cells by redirecting certain metabolic pathways, notably improving mitochondrial function. MSCs generally have an anti-inflammatory effect in preclinical models of infection, particularly in the early phase of severe ventilated pneumonia, as illustrated by the animal model we have developed, and preliminary trials are currently underway in humans. The ability of CSMs to correct sepsis-induced immunosuppression has not yet been explored. Nevertheless, CSMs possess the ability to communicate with the inflammatory microenvironment in which they are found, conferring plasticity to their response.
We hypothesize that CSMs could correct certain immune and metabolic dysfunctions in circulating immune cells from patients with sepsis meeting severity criteria who are admitted to the intensive care unit.
Furthermore, priming (or prior stimulation) of CSMs could enable a more precise and personalized therapeutic approach, with the possibility of directing CSMs toward a pro-inflammatory (CSM1) or anti-inflammatory (CSM2) phenotype through prior incubation with specific agonists (LPS; IFN-γ/TNF, respectively) before their administration. Depending on the patient's immune status (pro-inflammatory or anti-inflammatory phase), such a personalized approach would optimize treatment with CSMs.
Patient or authorized representative, informed and having given consent
Age ≥ 18 years
Clinically or microbiologically documented infection
SOFA-2 score ≥ 2
Individuals not enrolled in or not eligible for a social security program
Individuals subject to a legal protection order
Pregnant women, women in labor, or breastfeeding women
cytostatic chemotherapy within the previous 3 months,
Patient with sepsis complicated by ARDS or septic shock
Cohort
Prospective
Blood sample
Biological/VaccineDrawing an EDTA tube
Blood sample
Biological/VaccineCollection of 5 heparinized tubes
Concentration of TNF-α in the supernatant from ex vivo co-incubation of whole blood collected on days 1-3 after admission to the intensive care unit (± CSMs), as measured by ELISA, following stimulation of immune cells with LPS
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