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      Neutrophils: Need for Standardized Nomenclature

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          Abstract

          Neutrophils are the most abundant innate immune cell with critical anti-microbial functions. Since the discovery of granulocytes at the end of the nineteenth century, the cells have been given many names including phagocytes, polymorphonuclear neutrophils (PMN), granulocytic myeloid derived suppressor cells (G-MDSC), low density neutrophils (LDN) and tumor associated neutrophils (TANS). This lack of standardized nomenclature for neutrophils suggest that biologically distinct populations of neutrophils exist, particularly in disease, when in fact these may simply be a manifestation of the plasticity of the neutrophil as opposed to unique populations. In this review, we profile the surface markers and granule expression of each stage of granulopoiesis to offer insight into how each stage of maturity may be identified. We also highlight the remarkable surface marker expression profiles between the supposed neutrophil populations.

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          Most cited references156

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          Neutrophil extracellular traps kill bacteria.

          Neutrophils engulf and kill bacteria when their antimicrobial granules fuse with the phagosome. Here, we describe that, upon activation, neutrophils release granule proteins and chromatin that together form extracellular fibers that bind Gram-positive and -negative bacteria. These neutrophil extracellular traps (NETs) degrade virulence factors and kill bacteria. NETs are abundant in vivo in experimental dysentery and spontaneous human appendicitis, two examples of acute inflammation. NETs appear to be a form of innate response that binds microorganisms, prevents them from spreading, and ensures a high local concentration of antimicrobial agents to degrade virulence factors and kill bacteria.
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            Neutrophil recruitment and function in health and inflammation.

            Neutrophils have traditionally been thought of as simple foot soldiers of the innate immune system with a restricted set of pro-inflammatory functions. More recently, it has become apparent that neutrophils are, in fact, complex cells capable of a vast array of specialized functions. Although neutrophils are undoubtedly major effectors of acute inflammation, several lines of evidence indicate that they also contribute to chronic inflammatory conditions and adaptive immune responses. Here, we discuss the key features of the life of a neutrophil, from its release from bone marrow to its death. We discuss the possible existence of different neutrophil subsets and their putative anti-inflammatory roles. We focus on how neutrophils are recruited to infected or injured tissues and describe differences in neutrophil recruitment between different tissues. Finally, we explain the mechanisms that are used by neutrophils to promote protective or pathological immune responses at different sites.
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              Polarization of tumor-associated neutrophil phenotype by TGF-beta: "N1" versus "N2" TAN.

              TGF-beta blockade significantly slows tumor growth through many mechanisms, including activation of CD8(+) T cells and macrophages. Here, we show that TGF-beta blockade also increases neutrophil-attracting chemokines, resulting in an influx of CD11b(+)/Ly6G(+) tumor-associated neutrophils (TANs) that are hypersegmented, more cytotoxic to tumor cells, and express higher levels of proinflammatory cytokines. Accordingly, following TGF-beta blockade, depletion of these neutrophils significantly blunts antitumor effects of treatment and reduces CD8(+) T cell activation. In contrast, in control tumors, neutrophil depletion decreases tumor growth and results in more activated CD8(+) T cells intratumorally. Together, these data suggest that TGF-beta within the tumor microenvironment induces a population of TAN with a protumor phenotype. TGF-beta blockade results in the recruitment and activation of TANs with an antitumor phenotype.
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                Author and article information

                Contributors
                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                15 April 2021
                2021
                : 12
                : 602963
                Affiliations
                [1] 1 Discipline of Paediatrics, Trinity College, The University of Dublin , Dublin, Ireland
                [2] 2 Paediatric Research Laboratory, Trinity Translational Medicine Institute (TTMI), St James’ Hospital , Dublin, Ireland
                [3] 3 Trinity Health Kidney Centre, TTMI, Trinity College , Dublin, Ireland
                [4] 4 Viral Immunology Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute , Dublin, Ireland
                [5] 5 Neonatology, Coombe Women and Infant’s University Hospital , Dublin, Ireland
                [6] 6 National Children’s Research Centre , Dublin, Ireland
                [7] 7 Viral Immunology Group, Royal College of Surgeons in Ireland‐Medical University of Bahrain , Zallaq, Bahrain
                [8] 8 Irish Centre for Vascular Biology, Trinity College Dublin , Dublin, Ireland
                [9] 9 Neonatology, Children’s Hospital Ireland (CHI) at Crumlin , Dublin, Ireland
                [10] 10 Paediatrics, CHI at Tallaght, Tallaght University Hospital , Dublin, Ireland
                Author notes

                Edited by: Sonja Vermeren, University of Edinburgh, United Kingdom

                Reviewed by: Carsten Krieg, Medical University of South Carolina, United States; Zvi Granot, Hebrew College, United States

                *Correspondence: Eleanor J. Molloy, Eleanor.molloy@ 123456tcd.ie

                This article was submitted to Molecular Innate Immunity, a section of the journal Frontiers in Immunology

                Article
                10.3389/fimmu.2021.602963
                8081893
                33936029
                df4c556c-6adf-4cdf-a6cb-fb6ff14defe3
                Copyright © 2021 McKenna, Mhaonaigh, Wubben, Dwivedi, Hurley, Kelly, Stevenson, Little and Molloy

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 04 September 2020
                : 17 March 2021
                Page count
                Figures: 2, Tables: 3, Equations: 0, References: 156, Pages: 14, Words: 6183
                Categories
                Immunology
                Review

                Immunology
                neutrophils,granulopoiesis,neutrophil granules,low density neutrophils,nomenclature
                Immunology
                neutrophils, granulopoiesis, neutrophil granules, low density neutrophils, nomenclature

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