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.

Angiotensin converting enzyme inhibitors and angiotensin II receptor antagonist attenuate tumor growth via polarization of neutrophils toward an antitumor phenotype

“…Neutrophils are known to polarize into protumoral phenotype in tumor-bearing hosts 16,17 and most of these immunosuppressive neutrophils are found in the spleen and tumors. 1,15 Consistent with these findings, we found that splenic and intratumoral neutrophils from control tumorbearing mice showed significant differences in surface marker expression compared with those from naive mice. Splenic neutrophils from control tumor-bearing mice showed the decreased expression of CD16 (Fcg receptor III), CD55 (Decay-accelerating factor), CD88 (C5a receptor), CD120a/b (TNF receptor), CD256 (TNF ligand superfamily member 13), CD137 (CD137, a TNF receptor family member), CD101 (immunoglobulin superfamily member 2), CD80 (co-stimulating molecule), and the increased expression of CD43 (leukosialin) and CD98 (large neutral amino acid transporter).…”

“…Neutrophils have been reported to gain more segments during differentiation; thus, hypersegmented neutrophils could represent "old" neutrophils. 15 Thus, we examined the effect of captopril on neutrophil survival. Neutrophils were exposed to 500 mM captopril for 12 h, and survival rates were determined using annexin V/propidium iodide (PI) staining.…”

“…15,34 Therefore, we examined the different phenotypes of neutrophils by evaluating the surface expression of a number of markers (Fig. 5).…”

“…G-MDSCs suppress the immune response in tumorbearing hosts by expressing high levels of arginase 1 and facilitate tumor progression, invasion and metastasis. 2,[13][14][15] Recently, regulation of neutrophil plasticity in the tumor microenvironment has been reported. 16, 17 Fridlender et al 16 demonstrated the existence of dual neutrophil phenotypes within tumors: N1 (antitumoral) and N2 (protumoral) tumor-associated neutrophils (TANs).…”

Microbe-Specific Unconventional T Cells Induce Human Neutrophil Differentiation into Antigen Cross-Presenting Cells

“…As such, neutrophils regulate the recruitment and function of various cell types and interact with immune and nonimmune cells. Intriguingly, neutrophils directly affect Ag-specific responses by facilitating monocyte differentiation and dendritic cell maturation, and by interacting with T cells and B cells (4)(5)(6)(7)(8)(9)(10). Murine neutrophils have been shown to present Ags to both CD4 + and CD8 + T cells (11)(12)(13), and to differentiate into neutrophil-dendritic cell hybrids in vitro and in vivo (14,15).…”