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      Osteomyelitis is associated with increased anti-inflammatory response and immune exhaustion

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          Abstract

          Introduction

          Osteomyelitis (OMS) is a bone infection causing bone pain and severe complications. A balanced immune response is critical to eradicate infection without harming the host, yet pathogens manipulate immunity to establish a chronic infection. Understanding OMS-driven inflammation is essential for disease management, but comprehensive data on immune profiles and immune cell activation during OMS are lacking.

          Methods

          Using high-dimensional flow cytometry, we investigated the detailed innate and adaptive systemic immune cell populations in OMS and age- and sex-matched controls.

          Results

          Our study revealed that OMS is associated with increased levels of immune regulatory cells, namely T regulatory cells, B regulatory cells, and T follicular regulatory cells. In addition, the expression of immune activation markers HLA-DR and CD86 was decreased in OMS, while the expression of immune exhaustion markers TIM-3, PD-1, PD-L1, and VISTA was increased. Members of the T follicular helper (Tfh) cell family as well as classical and typical memory B cells were significantly increased in OMS individuals. We also found a strong correlation between memory B cells and Tfh cells.

          Discussion

          We conclude that OMS skews the host immune system towards the immunomodulatory arm and that the Tfh memory B cell axis is evident in OMS. Therefore, immune-directed therapies may be a promising alternative for eradication and recurrence of infection in OMS, particularly in individuals and areas where antibiotic resistance is a major concern.

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          Most cited references66

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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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            Recommendations for myeloid-derived suppressor cell nomenclature and characterization standards

            Myeloid-derived suppressor cells (MDSC) are a heterogeneous population expanded in cancer and other chronic inflammatory conditions. Here the authors identify the challenges and propose a set of minimal reporting guidelines for mouse and human MDSC.
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              The diverse functions of the PD1 inhibitory pathway

              T cell activation is a highly regulated process involving peptide-MHC engagement of the T cell receptor and positive costimulatory signals. Upon activation, coinhibitory 'checkpoints', including programmed cell death protein 1 (PD1), become induced to regulate T cells. PD1 has an essential role in balancing protective immunity and immunopathology, homeostasis and tolerance. However, during responses to chronic pathogens and tumours, PD1 expression can limit protective immunity. Recently developed PD1 pathway inhibitors have revolutionized cancer treatment for some patients, but the majority of patients do not show complete responses, and adverse events have been noted. This Review discusses the diverse roles of the PD1 pathway in regulating immune responses and how this knowledge can improve cancer immunotherapy as well as restore and/or maintain tolerance during autoimmunity and transplantation.
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                Author and article information

                Contributors
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                URI : https://loop.frontiersin.org/people/798262Role: Role: Role: Role: Role: Role: Role: Role: Role:
                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                26 April 2024
                2024
                : 15
                : 1396592
                Affiliations
                [1] 1 Department of Orthopedics and Trauma Surgery, University Hospital Bonn , Bonn, Germany
                [2] 2 Department of Hand, Plastic and Reconstructive Surgery, Burn Center, BG Trauma Center Ludwigshafen, University of Heidelberg , Ludwigshafen, Germany
                [3] 3 Institute of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn , Bonn, Germany
                [4] 4 Transplantation Research Center, Renal Division, Brigham and Women’s Hospital, Harvard Medical School , Boston, MA, United States
                Author notes

                Edited by: Leonardo M. R. Ferreira, Medical University of South Carolina, United States

                Reviewed by: Fairuz Faizee, University of Toledo, United States

                Meenal Mehrotra, Medical University of South Carolina, United States

                *Correspondence: Frank A. Schildberg, frank.schildberg@ 123456ukbonn.de

                †These authors share first authorship

                ‡These authors share last authorship

                Article
                10.3389/fimmu.2024.1396592
                11082283
                d6d4727b-c8e0-46db-8cc8-95a1fced14d5
                Copyright © 2024 Surendar, Hackenberg, Schmitt-Sánchez, Ossendorff, Welle, Stoffel-Wagner, Sage, Burger, Wirtz, Strauss and Schildberg

                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
                : 06 March 2024
                : 12 April 2024
                Page count
                Figures: 10, Tables: 1, Equations: 0, References: 66, Pages: 15, Words: 6739
                Funding
                Funded by: Deutsche Forschungsgemeinschaft , doi 10.13039/501100001659;
                Funded by: John Templeton Foundation , doi 10.13039/100000925;
                The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy – EXC2151 – 390873048 and the John Templeton Foundation (grant #62214).
                Categories
                Immunology
                Original Research
                Custom metadata
                Immunological Tolerance and Regulation

                Immunology
                osteomyelitis,infection,inflammation,immune exhaustion,t follicular helper cells,musculoskeletal immunology

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