Immune suppression by neutrophils and granulocytic myeloid-derived suppressor cells: similarities and differences

Abstract

Neutrophils are essential effector cells in the host defense against invading pathogens. Recently, novel neutrophil functions have emerged in addition to their classical anti-microbial role. One of these functions is the suppression of T cell responses. In this respect, neutrophils share similarities with granulocytic myeloid-derived suppressor cells (G-MDSCs). In this review, we will discuss the similarities and differences between neutrophils and G-MDSCs. Various types of G-MDSCs have been described, ranging from immature to mature cells shaping the immune response by different immune suppressive mechanisms. However, all types of G-MDSCs share distinct features of neutrophils, such as surface markers and morphology. We propose that G-MDSCs are heterogeneous and represent novel phenotypes of neutrophils, capable of suppressing the immune response. In this review, we will attempt to clarify the differences and similarities between neutrophils and G-MDSCs and attempt to facilitate further research.

Figures

Fig. 1

Priming versus functional phenotypes of neutrophils. This figure illustrates that phenotypes are defined as cells that retain specialized functions for a prolonged time. Priming refers to the mechanism that is rapidly and reversibly induced by soluble or cell associated mediators such as platelet activating factor (PAF) [7], which potentiate functions of neutrophils but do not change their overall function. Priming can potentiate all different phenotypes and functions, such as migration, production of ROS and phagocytosis

Fig. 2

Schematic representations and images of the nuclear morphology of human and murine neutrophils during subsequent stages of development. Myelocytes mature into metamyelocytes, banded neutrophils, and finally into mature segmented neutrophils. Neutrophils may also become hypersegmented, with more than 4 nuclear lobes (human) or a cloverleaf shape (mouse). It is unknown whether hypersegmented neutrophils are more mature than segmented neutrophils

Fig. 3

Mechanisms of suppression by G-MDSCs and suppressive neutrophils. Suppression can be mediated by extracellular arginase, extracellular ROS, or ROS in an immunological synapse. Al these mechanisms result in reduced T cell proliferation, via decreases in extracellular l-arginine, cofilin, TCRζ expression, NF-κB activation, or unknown mechanisms

Fig. 4

The origin of G-MDSCs remains unknown. Hypothetically, these calls can arise from mature (1) or immature (2) neutrophils receiving signals to become suppressive. Alternatively, there may be a dedicated granulopoiesis, which only produces suppressive cells. This granulopoiesis can take place either in the bone marrow (3) or extramedullary (4). Additionally, these cells can be immature (i), mature (m) or hypersegmented (h)