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Sepsis is a major cause of death in the Western world with high mortality rates in ICUs. The disease is characterized by an excessive and dysregulated immune response to microbial infections, coagulation abnormalities leading to capillary leakage, lung damage, and finally, multiple organ failure [1]. It is known that most septic patients in ICUs, in addition to hyperinflammatory response, suffer from a hypoinflammatory state, which often leads to sepsis-induced multiorgan dysfunction and death. This suggests that sepsis-induced immunosuppression is a significant factor contributing to these deaths. MDSCs may be a critical element in the development of such a hypoinflammatory state and thus, in the outcome of the disease.

Although MDSCs were described originally in cancer [2], it has now become increasingly clear that MDSCs play an important role in the regulation of immune responses in many pathological conditions not directly associated with cancer. MDSCs are pathologically activated immature myeloid cells comprised of immature neutrophils, monocytes, and myeloid precursors. It is important to point out that the immature state and myeloid origin are necessary, but not sufficient, characteristics to define MDSCs. These cells have rather unique genetic and biochemical features and most importantly, the ability to inhibit immune responses by using a large array of different mechanisms. MDSCs consist of two main subsets: PMN-MDSC and M-MDSC. The phenotype of these populations is now well defined in mice and humans. PMN-MDSCs consist of relatively immature and pathologically activated neutrophils and are defined in mice as CD11b+Ly6ClowLy6G+ cells, whereas M-MDSCs, pathologically activated inflammatory monocytes, are defined as CD11b+Ly6ChighLy6G− cells. Historically, human MDSCs were defined as lineage marker (CD3, CD14, CD19, CD56)-negative, HLA-DR−, and common myeloid marker CD33-positive cells, copurified with mononuclear cells on a ficoll gradient. More recently, the existence of two subsets of cells (similar to murine models) has been reported, and PMN-MDSCs are commonly characterized as CD11b+CD14− cells expressing a granulocytic marker: CD15 or CD66b. M-MDSCs are most commonly defined by two combinations of markers: CD11b+CD14−CD15− (or CD66b−) or CD11b+CD14+HLA-DR−/lo. It appears that at least in cancer, M-MDSCs may play a central role in the development of immune-suppressive myeloid cells. In tumor sites, they differentiate to tumor-associated macrophages with potent immune-suppressive activity and in the periphery, may give rise to PMN-MDSCs.

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