Recherche translationnelle française à la Une : Dérivés granulocytaires et prédisposition aux infections !

L’équipe de Réanimation Médicale du CHU de Rennes à la une avec un article récemment publié dans AJRCCM :

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Early Expansion of Circulating Granulocytic Myeloid-derived Suppressor Cells Predicts Development of Nosocomial Infections in Patients with Sepsis

Fabrice Uhel 1,2,3,4, Imane Azzaoui 3,4, Murielle Grégoire 3,4, Céline Pangault 3,4, Joelle Dulong 3,4, Jean-Marc Tadié 1,2,3,4, Arnaud Gacouin 1,2, Christophe Camus 1,2, Luc Cynober 5,6, Thierry Fest 3,4, Yves Le Tulzo 1,2,3,4, et al.

Rationale: Sepsis induces a sustained immune dysfunction responsible for poor outcome and nosocomial infections. Myeloid-derived suppressor cells (MDSCs) described in cancer and inflammatory processes may be involved in sepsis-induced immune suppression, but their clinical impact remains poorly defined.

Objectives: To clarify phenotype, suppressive activity, origin, and clinical impact of MDSCs in patients with sepsis.

Methods: Peripheral blood transcriptomic analysis was performed on 29 patients with sepsis and 15 healthy donors. A second cohort of 94 consecutive patients with sepsis, 11 severity-matched intensive care patients, and 67 healthy donors was prospectively enrolled for flow cytometry and functional experiments.

Measurements and Main Results: Genes involved in MDSC suppressive functions, including S100A12, S100A9, MMP8, and ARG1, were up-regulated in the peripheral blood of patients with sepsis. CD14posHLA-DRlow/neg monocytic (M)-MDSCs were expanded in intensive care unit patients with and without sepsis and CD14negCD15pos low-density granulocytes/granulocytic (G)-MDSCs were more specifically expanded in patients with sepsis (P < 0.001). Plasma levels of MDSC mediators S100A8/A9, S100A12, and arginase 1 were significantly increased. In vitro, CD14pos– and CD15pos-cell depletion increased T-cell proliferation in patients with sepsis. G-MDSCs, made of immature and mature granulocytes expressing high levels of degranulation markers, were specifically responsible for arginase 1 activity. High initial levels of G-MDSCs, arginase 1, and S100A12 but not M-MDSCs were associated with subsequent occurrence of nosocomial infections.

Conclusions: M-MDSCs and G-MDSCs strongly contribute to T-cell dysfunction in patients with sepsis. More specifically, G-MDSCs producing arginase 1 are associated with a higher incidence of nosocomial infections and seem to be major actors of sepsis-induced immune suppression.

Keywords: sepsis; granulocytes; monocytes; cross infection; immune tolerance
Dernière mise à jour : 19/09/2017

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