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      The Role of Macrophages in Staphylococcus aureus Infection

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          Abstract

          Staphylococcus aureus is a member of the human commensal microflora that exists, apparently benignly, at multiple sites on the host. However, as an opportunist pathogen it can also cause a range of serious diseases. This requires an ability to circumvent the innate immune system to establish an infection. Professional phagocytes, primarily macrophages and neutrophils, are key innate immune cells which interact with S. aureus, acting as gatekeepers to contain and resolve infection. Recent studies have highlighted the important roles of macrophages during  S. aureus infections, using a wide array of killing mechanisms. In defense,  S. aureus has evolved multiple strategies to survive within, manipulate and escape from macrophages, allowing them to not only subvert but also exploit this key element of our immune system. Macrophage- S. aureus interactions are multifaceted and have direct roles in infection outcome. In depth understanding of these host-pathogen interactions may be useful for future therapeutic developments. This review examines macrophage interactions with  S. aureus throughout all stages of infection, with special emphasis on mechanisms that determine infection outcome.

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          Most cited references441

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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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            Staphylococcus aureus infections: epidemiology, pathophysiology, clinical manifestations, and management.

            Staphylococcus aureus is a major human pathogen that causes a wide range of clinical infections. It is a leading cause of bacteremia and infective endocarditis as well as osteoarticular, skin and soft tissue, pleuropulmonary, and device-related infections. This review comprehensively covers the epidemiology, pathophysiology, clinical manifestations, and management of each of these clinical entities. The past 2 decades have witnessed two clear shifts in the epidemiology of S. aureus infections: first, a growing number of health care-associated infections, particularly seen in infective endocarditis and prosthetic device infections, and second, an epidemic of community-associated skin and soft tissue infections driven by strains with certain virulence factors and resistance to β-lactam antibiotics. In reviewing the literature to support management strategies for these clinical manifestations, we also highlight the paucity of high-quality evidence for many key clinical questions.
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              Regulation of type I interferon responses.

              Type I interferons (IFNs) activate intracellular antimicrobial programmes and influence the development of innate and adaptive immune responses. Canonical type I IFN signalling activates the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway, leading to transcription of IFN-stimulated genes (ISGs). Host, pathogen and environmental factors regulate the responses of cells to this signalling pathway and thus calibrate host defences while limiting tissue damage and preventing autoimmunity. Here, we summarize the signalling and epigenetic mechanisms that regulate type I IFN-induced STAT activation and ISG transcription and translation. These regulatory mechanisms determine the biological outcomes of type I IFN responses and whether pathogens are cleared effectively or chronic infection or autoimmune disease ensues.
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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
                19 January 2021
                2020
                : 11
                : 620339
                Affiliations
                [1] 1 Department of Molecular Biology and Biotechnology, University of Sheffield , Sheffield, United Kingdom
                [2] 2 Florey Institute, University of Sheffield , Sheffield, United Kingdom
                [3] 3 The Bateson Centre, University of Sheffield , Sheffield, United Kingdom
                [4] 4 Department of Infection, Immunity and Cardiovascular Disease, Medical School, University of Sheffield , Sheffield, United Kingdom
                Author notes

                Edited by: Rachel McLoughlin, Trinity College Dublin, Ireland

                Reviewed by: Dane Parker, The State University of New Jersey, United States; David Heinrichs, Western University, Canada

                *Correspondence: Simon J. Foster, s.foster@ 123456sheffield.ac.uk

                †These authors share first authorship

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

                Article
                10.3389/fimmu.2020.620339
                7850989
                33542723
                5a4ad5c8-9720-4dbf-98e8-0c707d5b608a
                Copyright © 2021 Pidwill, Gibson, Cole, Renshaw and Foster

                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
                : 22 October 2020
                : 02 December 2020
                Page count
                Figures: 5, Tables: 0, Equations: 0, References: 441, Pages: 30, Words: 14347
                Funding
                Funded by: Medical Research Council 10.13039/501100000265
                Award ID: MR/R001111/1
                Funded by: Medical Research Council 10.13039/501100000265
                Award ID: MRNO2995X/1
                Categories
                Immunology
                Review

                Immunology
                macrophage,staphylococcus,phagocytosis,immunity,immune evasion
                Immunology
                macrophage, staphylococcus, phagocytosis, immunity, immune evasion

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