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      Neutrophils—From Bone Marrow to First-Line Defense of the Innate Immune System

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          Abstract

          Neutrophils (polymorphonuclear cells; PMNs) form a first line of defense against pathogens and are therefore an important component of the innate immune response. As a result of poorly controlled activation, however, PMNs can also mediate tissue damage in numerous diseases, often by increasing tissue inflammation and injury. According to current knowledge, PMNs are not only part of the pathogenesis of infectious and autoimmune diseases but also of conditions with disturbed tissue homeostasis such as trauma and shock. Scientific advances in the past two decades have changed the role of neutrophils from that of solely immune defense cells to cells that are responsible for the general integrity of the body, even in the absence of pathogens. To better understand PMN function in the human organism, our review outlines the role of PMNs within the innate immune system. This review provides an overview of the migration of PMNs from the vascular compartment to the target tissue as well as their chemotactic processes and illuminates crucial neutrophil immune properties at the site of the lesion. The review is focused on the formation of chemotactic gradients in interaction with the extracellular matrix (ECM) and the influence of the ECM on PMN function. In addition, our review summarizes current knowledge about the phenomenon of bidirectional and reverse PMN migration, neutrophil microtubules, and the microtubule organizing center in PMN migration. As a conclusive feature, we review and discuss new findings about neutrophil behavior in cancer environment and tumor tissue.

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          Most cited references398

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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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            Cancer-related inflammation.

            The mediators and cellular effectors of inflammation are important constituents of the local environment of tumours. In some types of cancer, inflammatory conditions are present before a malignant change occurs. Conversely, in other types of cancer, an oncogenic change induces an inflammatory microenvironment that promotes the development of tumours. Regardless of its origin, 'smouldering' inflammation in the tumour microenvironment has many tumour-promoting effects. It aids in the proliferation and survival of malignant cells, promotes angiogenesis and metastasis, subverts adaptive immune responses, and alters responses to hormones and chemotherapeutic agents. The molecular pathways of this cancer-related inflammation are now being unravelled, resulting in the identification of new target molecules that could lead to improved diagnosis and treatment.
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              Pattern recognition receptors and inflammation.

              Infection of cells by microorganisms activates the inflammatory response. The initial sensing of infection is mediated by innate pattern recognition receptors (PRRs), which include Toll-like receptors, RIG-I-like receptors, NOD-like receptors, and C-type lectin receptors. The intracellular signaling cascades triggered by these PRRs lead to transcriptional expression of inflammatory mediators that coordinate the elimination of pathogens and infected cells. However, aberrant activation of this system leads to immunodeficiency, septic shock, or induction of autoimmunity. In this Review, we discuss the role of PRRs, their signaling pathways, and how they control inflammatory responses. 2010 Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                URI : https://loop.frontiersin.org/people/1460398
                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                23 December 2021
                2021
                : 12
                : 767175
                Affiliations
                [1] Department of Anesthesiology, University Medical Center Regensburg , Regensburg, Germany
                Author notes

                Edited by: Deirdre R. Coombe, Curtin University, Australia

                Reviewed by: Benyamin Rosental, Ben-Gurion University of the Negev, Israel; Charles W. Frevert, University of Washington Tacoma, United States

                *Correspondence: Richard Felix Kraus, Richard-Felix.Kraus@ 123456stud.uni-regensburg.de

                This article was submitted to Inflammation, a section of the journal Frontiers in Immunology

                †ORCID: Richard Felix Kraus, orcid.org/0000-0001-5280-6530; Michael Andreas Gruber, orcid.org/0000-0002-5509-9760

                Article
                10.3389/fimmu.2021.767175
                8732951
                35003081
                44276baa-c74b-49fb-8ff5-687645114cdb
                Copyright © 2021 Kraus and Gruber

                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
                : 30 August 2021
                : 03 December 2021
                Page count
                Figures: 7, Tables: 3, Equations: 0, References: 399, Pages: 35, Words: 16786
                Categories
                Immunology
                Review

                Immunology
                microtubule organization center,netosis,tumor association,neutrophil (pmn) function,neutrophil extravasation,extracellular matrix (ecm),chemotactic gradients,bidirectional (trans)migration

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