Format

Send to

Choose Destination
Am J Respir Crit Care Med. 2017 Aug 1;196(3):315-327. doi: 10.1164/rccm.201606-1143OC.

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

Uhel F1,2,3,4, Azzaoui I3,4, Grégoire M3,4, Pangault C3,4, Dulong J3,4, Tadié JM1,2,3,4, Gacouin A1,2, Camus C1,2, Cynober L5,6, Fest T3,4, Le Tulzo Y1,2,3,4, Roussel M3,4, Tarte K3,4.

Author information

1
1 Centre Hospitalier Universitaire Rennes, Maladies Infectieuses et Réanimation Médicale, Rennes, France.
2
2 Institut National de la Santé et de la Recherche Médicale, Centre d'Investigation Clinique-1414, and.
3
3 Unité Mixte de Recherche U917, Institut National de la Santé et de la Recherche Médicale, Université Rennes 1, Etablissement Français du Sang Bretagne, Rennes, France.
4
4 Centre Hospitalier Universitaire Rennes, Laboratoire Suivi Immunologique des Thérapeutiques Innovantes, Rennes, France.
5
5 Assistance Publique-Hôpitaux de Paris Hôpital Cochin, Service de Biochimie, and.
6
6 Département de Nutrition Equipe d'Accueil 4466, Faculté de Pharmacie, Université Paris Descartes, Paris, France.

Abstract

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:

cross infection; granulocytes; immune tolerance; monocytes; sepsis

PMID:
28146645
DOI:
10.1164/rccm.201606-1143OC
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Atypon
Loading ...
Support Center