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      Microbicidal Phagocytosis of Nucleus Pulposus Cells Against Staphylococcus aureus via the TLR2/MAPKs Signaling Pathway

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          Abstract

          Intervertebral disc (IVD) is an immune-privileged organ that lacks immunocytes, such as macrophages or neutrophils; therefore, it is unclear how IVD immunological defense against bacterial infection occurs. Here, we demonstrated that nucleus pulposus cells (NPCs), the vital machinery for maintaining the homeostasis of IVD, exerted microbicidal activity against Staphylococcus aureus via induction of phagolysosome formation. Moreover, we found that the Toll-like receptor 2 (TLR2)/mitogen-activated protein kinases (MAPKs) signaling pathway is critical for bacterial phagocytosis and phagolysosome formation of NPCs. These findings demonstrated for the first time that NPCs could function as non-professional phagocytes against S. aureus infection, thereby enhancing antimicrobial defense against bacterial infections in IVDs.

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          Most cited references34

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          Corpse clearance defines the meaning of cell death.

          While philosophers seek the meaning of life, cell biologists are becoming ever more interested in the meaning of death. Apoptosis marks unwanted cells with 'eat me' signals that direct recognition, engulfment and degradation by phagocytes. Far from being the end of the story, these clearance events allow scavenger cells to confer meaning upon cell death. But if the phagocytic 'spin doctors' receive or transmit the wrong messages, trouble ensues.
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            Phagocytosis: elegant complexity.

            Phagocytosis requires receptor-mediated recognition of particles, usually in the guise of infectious agents and apoptotic cells. Phagosomes fuse with lysosomes to generate phagolysosomes, which play a key role in enzymatic digestion of the internalized contents into component parts. Recent findings indicate that a simple paradigm of a single cognate receptor interaction that guides the phagosome to phagolysosome formation belies the complexity of combinatorial receptor recognition and diversity of phagosome function. In fact, phagosomes are comprised of hundreds of proteins that play a key role in deciphering the contents of the phagosome and in defining host response. In this review we discuss how the challenge of recognizing diverse molecular patterns is met by combinatorial interactions between phagocytic receptors. Furthermore, these combinations are dynamic and both sculpt the balance between a proinflammatory or anti-inflammatory response and direct phagosome diversity. We also indicate an important role for genetically tractable model organisms in defining key components of this evolutionarily conserved process.
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              Phagosome maturation: aging gracefully.

              Foreign particles and apoptotic bodies are eliminated from the body by phagocytic leucocytes. The initial stage of the elimination process is the internalization of the particles into a plasma membrane-derived vacuole known as the phagosome. Such nascent phagosomes, however, lack the ability to kill pathogens or to degrade the ingested targets. These properties are acquired during the course of phagosomal maturation, a complex sequence of reactions that result in drastic remodelling of the phagosomal membrane and contents. The determinants and consequences of the fusion and fission reactions that underlie phagosomal maturation are the topic of this review.
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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
                22 May 2019
                2019
                : 10
                : 1132
                Affiliations
                [1] 1Department of Orthopedics, Kunshan Hospital of Traditional Chinese Medicine , Kunshan, China
                [2] 2Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases With Integrated Chinese-Western Medicine, Ruijin Hospital, Shanghai Institute of Traumatology and Orthopedics, Shanghai Jiaotong University School of Medicine , Shanghai, China
                [3] 3Department of Oncology, The Affiliated Hospital of Qingdao University , Qingdao, China
                [4] 4Kunshan Hospital of Traditional Chinese Medicine , Kunshan, China
                [5] 5Department of Orthopedics, Ruijin Hospital North, Shanghai Jiaotong University School of Medicine , Shanghai, China
                [6] 6Department of Medical Microbiology and Parasitology, Shanghai Jiaotong University School of Medicine , Shanghai, China
                Author notes

                Edited by: Juarez Antonio Simões Quaresma, Instituto Evandro Chagas, Brazil

                Reviewed by: Benjamin Gantenbein, University of Bern, Switzerland; Wenbin Hua, Wuhan Union Hospital, China; Wei Ye, Sun Yat-sen University, China

                *Correspondence: Changwei Li changwei393331@ 123456163.com

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

                †These authors have contributed equally to this work

                Article
                10.3389/fimmu.2019.01132
                6538773
                31178866
                91582ebf-6ce9-4215-874e-91405318acfc
                Copyright © 2019 Lin, Cong, Liu, Jiao, Yuan, Tang, Chen, Zheng, Xiao, Li, Chen and Cao.

                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 January 2019
                : 07 May 2019
                Page count
                Figures: 5, Tables: 0, Equations: 0, References: 40, Pages: 10, Words: 6914
                Categories
                Immunology
                Original Research

                Immunology
                nucleus pulposus cells,phagocytosis,phagolysosomes,staphylococcus aureus,tlr2,mapks
                Immunology
                nucleus pulposus cells, phagocytosis, phagolysosomes, staphylococcus aureus, tlr2, mapks

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