No abstract

Neutrophils and polymorphonucler myeloid-derived suppressor cells (PMN-MDSC) share origin and many morphological and phenotypic features. However, they have different biological role. Neutrophils are one of the major mechanisms of protection against invading pathogens, whereas PMN-MDSC have immune suppressive activity and restrict immune responses in cancer, chronic infectious disease, trauma, sepsis, and many other pathological conditions. Although in healthy adult individuals, PMN-MDSC are not or barely detectable, in patients with cancer and many other diseases they accumulate at various degree and co-exist with neutrophils. Recent advances allow for better distinction of these cells and better understanding of their biological role. Accumulating evidence indicates PMN-MDSC as pathologically activated neutrophils, with important role in regulation of immune responses. In this review, we provide an overview on the definition and characterization of PMN-MDSC and neutrophils, their pathological significance in a variety of diseases, and their interaction with other stromal components.

Myeloid-derived suppressor cells (MDSC) are pathologically activated and relatively immature myeloid cells, which are implicated in the immune regulation of many pathologic conditions1,2. Phenotypically and morphologically MDSC are similar to neutrophils (PMN-MDSC) and monocytes (M-MDSC). However, they have potent suppressive activity, a distinct gene expression profile, and biochemical characteristics3. None or very few MDSC are observed in steady state physiological conditions. Therefore, until recently, accumulation of MDSC was considered as a consequence of pathological process or pregnancy. Here, we report that MDSC with a potent ability to suppress T cells are present during the first weeks of life in mice and humans. MDSC suppressive activity was triggered by lactoferrin and mediated by nitric oxide, PGE2, and S100A9/A8 proteins. Newborn MDSC had a transcriptome similar to that of tumor MDSC, but with a strong up-regulation of an antimicrobial gene network and had potent antibacterial activity. MDSC played a critical role in control of experimental necrotizing enterocolitis (NEC) in newborn mice. MDSC in infants with very low-weight, which are prone to the development of NEC, had lower MDSC levels and suppressive activity than infants with normal weight. Thus, the transitory presence of MDSC may be critical for regulation of inflammation in newborns.