What about the neutrophils phenotypes?

Human neutrophils are in the sights of immunology, since recent research has positioned them as new players in adaptive immunity besides innate immunity. These leukocytes not only limit their function to phagocytosis, production of reactive oxygen species and generation of neutrophil extracellular traps, but also modulate the immune response according to the microenvironment and the cell-cell interactions, such as interactions between neutrophils, T cells and macrophages. This review summarizes current polymorphonuclear neutrophils research on some phenotypes in scientific literature in murine and human models. Correspondence to: Novak ITC, Institute of Cell Biology, Faculty of Medical Sciences, National University of Cordoba, Argentina, Tel: 00 54 351 433 4020; E-mail: inovak@cmefcm.uncor.edu


Introduction
Polymorphonuclear (PMN) neutrophils are leukocytes that not only limit their function to phagocytosis, production of reactive oxygen species (ROS) and generation of neutrophil extracellular traps (NETs), but also modulate the immune response according to the microenvironment where they are and according to the interaction they establish with others cell types. Neutrophils have a role in the activation and regulation of innate and adaptive immunity [1]. The variability of its functions according to its environment, physiological or pathological condition, and the expression of different surface markers have allowed to characterize different profiles of neutrophils in murine and human models.

Interaction between neutrophils, macrophages and T cells
In relation to the interaction between neutrophils and macrophages, PMNs contribute to the activation and recruitment of macrophages at the site of infection or in acute inflammation [2]. There is evidence of the existence of "proinflammatory" and "anti-inflammatory" neutrophil subsets that show a unique pattern of cytokine and chemokine production and they differ in receptor expression. It is possible that these "proinflammatory" and "anti-inflammatory" forms of neutrophils change the course of the immune response by inducing M1 or classically activated macrophages and M2 alternatively activated, respectively [3].
About possible interactions between T cells and neutrophils, the cytokines IL17A, IL17F secreted by Th17 cells (which play a prominent role in the immunity against extracellular bacteria and mycotic infections and have also been related to autoimmune phenomena) induce a rapid and massive infiltration of the affected tissue by the neutrophils. Reciprocally PMNs release of chemokines that attract T lymphocytes to the inflammation sites [4][5][6] and also cytokines that influence differentiation and proliferation of T cells [7][8][9]. Interestingly, a subset of neutrophils in human systemic inflammation inhibits T cell functions through Mac-1 [10]. PMN neutrophils can release extracellular traps (NETs) which trap and kill a variety of microbes, and they have been proposed with role in T cell sensitization (9). NETs have been implicated in cancer immunoediting [11]. This NETs are composed of chromatin, histone and granule proteins [12,13]. Recently has been reported costimulatory molecules CD80 and CD86 colocalized in NETs [14,15]. This finding would allow PMNs to exert function as APCs and modulatory functions of various subpopulations of T cells. Neutrophils and Th17 cells have been colocalized in tissues of the gut of patients with Crohn's disease and in synovial fluid of patients with rheumatoid arthritis, in tissues isolated from patients with asthma and in tissues infected with Helicobacter pylori [2]. Neutrophils isolated from synovial fluid of patients with rheumatoid arthritis express Class II Major Histocompatibility Complex (MHC) molecules [16].
Major histocompatibility complex class II (DR) antigen and costimulatory molecules are observed on in vitro and in vivo activated human PMN neutrophils [17]. Cytoplasmic reservoirs of costimulatory molecules B7: CD80 mainly within secretory vesicles and CD86 within secondary, azurophilic granules and secretory vesicles were described [17].
The initiation of adaptive immune responses requires the fundamental stage of antigen presentation to T lymphocytes and currently the area of contact between T cell and an antigen presenting cell is known as "immune synapse" (SI) [18][19][20]. In murine models, neutrophil differentiation to a hybrid cell population exhibiting a dual phenotype with neutrophil and dendritic cell function [21] was experimentally described. Other authors demonstrated Class II restricted antigens presentation [22,23]. Although some neutrophils have been described at sites of inflammation expressing MHC Class II molecules and T-cell costimulatory molecules in mice and humans, their origin, phenotype and function remain unclear [24].
It is known that PMN neutrophils are considered short-lived cells in humans, but in inflammation, they increase its longevity. In vitro studies on leukocyte interactions in samples from patients with serology positive for Chagas' disease, the extension of its longevity in cell culture was observed [25]. Recently has been reported costimulatory • high level immunosuppressive molecule programmed death-ligand 1 (PD-L1).
• Tumour-infiltrating PD-L1+ neutrophils exhibit immunosuppressive function and are correlated with disease stage and poor patient survival molecules and extracellular traps in patients with serology positive for Chagas' disease and that was related with autoimmunity phenomena [26]. Suppressive IL-10-producing neutrophils were found in this parasitosis in a murine model, reducing inflammation and mortality during T. cruzi infection through IL17RA-signaling [27].
This review attempts to synthesize the characteristics of PMN neutrophils, from some phenotypes observed in scientific works (Table 1).

Conclusion
Neutrophils are very interesting cells implicated in innate and adaptive immunity. There are many described phenotypes of PMN neutrophils, but there are heterogenea descriptions in literature, because parameters, methods, specie, tissue, biomarkers, are different. Anyway, these studies are very useful in the context of the one developed avoiding the extrapolation.