Myeloid-Derived Suppressor-like Cells as a Prognostic Marker in Critically Ill Patients: Insights from Experimental Endotoxemia and Intensive Care Patients
Irene T. Schrijver,
Jacobus Herderschee,
Charlotte Théroude,
Antonios Kritikos,
Guus Leijte,
Didier Le Roy,
Maelick Brochut,
Jean-Daniel Chiche,
Matthieu Perreau,
Giuseppe Pantaleo,
Benoit Guery,
Matthijs Kox,
Peter Pickkers,
Thierry Calandra,
Thierry Roger
Affiliations
Irene T. Schrijver
Infectious Diseases Service, Department of Medicine, Lausanne University Hospital and University of Lausanne, 1011 Lausanne, Switzerland
Jacobus Herderschee
Infectious Diseases Service, Department of Medicine, Lausanne University Hospital and University of Lausanne, 1011 Lausanne, Switzerland
Charlotte Théroude
Infectious Diseases Service, Department of Medicine, Lausanne University Hospital and University of Lausanne, 1011 Lausanne, Switzerland
Antonios Kritikos
Infectious Diseases Service, Department of Medicine, Lausanne University Hospital and University of Lausanne, 1011 Lausanne, Switzerland
Guus Leijte
Radboud Center for Infectious Diseases, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands
Didier Le Roy
Infectious Diseases Service, Department of Medicine, Lausanne University Hospital and University of Lausanne, 1011 Lausanne, Switzerland
Maelick Brochut
Infectious Diseases Service, Department of Medicine, Lausanne University Hospital and University of Lausanne, 1011 Lausanne, Switzerland
Jean-Daniel Chiche
Service of Adult Intensive Care Medicine, Lausanne University Hospital and University of Lausanne, 1011 Lausanne, Switzerland
Matthieu Perreau
Service of Immunology and Allergy, Department of Medicine, Lausanne University Hospital and University of Lausanne, 1010 Lausanne, Switzerland
Giuseppe Pantaleo
Service of Immunology and Allergy, Department of Medicine, Lausanne University Hospital and University of Lausanne, 1010 Lausanne, Switzerland
Benoit Guery
Infectious Diseases Service, Department of Medicine, Lausanne University Hospital and University of Lausanne, 1011 Lausanne, Switzerland
Matthijs Kox
Radboud Center for Infectious Diseases, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands
Peter Pickkers
Radboud Center for Infectious Diseases, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands
Thierry Calandra
Infectious Diseases Service, Department of Medicine, Lausanne University Hospital and University of Lausanne, 1011 Lausanne, Switzerland
Thierry Roger
Infectious Diseases Service, Department of Medicine, Lausanne University Hospital and University of Lausanne, 1011 Lausanne, Switzerland
Patients admitted to the intensive care unit (ICU) often experience endotoxemia, nosocomial infections and sepsis. Polymorphonuclear and monocytic myeloid-derived suppressor cells (PMN-MDSCs and M-MDSCs) can have an important impact on the development of infectious diseases, but little is known about their potential predictive value in critically ill patients. Here, we used unsupervised flow cytometry analyses to quantify MDSC-like cells in healthy subjects challenged with endotoxin and in critically ill patients admitted to intensive care units and at risk of developing infections. Cells phenotypically similar to PMN-MDSCs and M-MDSCs increased after endotoxin challenge. Similar cells were elevated in patients at ICU admission and normalized at ICU discharge. A subpopulation of M-MDSC-like cells expressing intermediate levels of CD15 (CD15int M-MDSCs) was associated with overall mortality (p = 0.02). Interestingly, the high abundance of PMN-MDSCs and CD15int M-MDSCs was a good predictor of mortality (p = 0.0046 and 0.014), with area under the ROC curve for mortality of 0.70 (95% CI = 0.4–1.0) and 0.86 (0.62–1.0), respectively. Overall, our observations support the idea that MDSCs represent biomarkers for sepsis and that flow cytometry monitoring of MDSCs may be used to risk-stratify ICU patients for targeted therapy.
