Human prosthetic joint infections are associated with myeloid-derived suppressor cells (MDSCs): Implications for infection persistence
| Autor: | Kevin L. Garvin, Curtis W. Hartman, Cortney E. Heim, Jessica Odvody, Debbie Vidlak, Tammy Kielian |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
education.field_of_study medicine.drug_class CD14 T cell Antibiotics CD33 Population Biology 03 medical and health sciences 030104 developmental biology Immune system medicine.anatomical_structure Immunology medicine Myeloid-derived Suppressor Cell Orthopedics and Sports Medicine Prosthesis-Related Infection education |
| Zdroj: | Journal of Orthopaedic Research®. 36:1605-1613 |
| ISSN: | 0736-0266 |
| Popis: | Prosthetic joint infection (PJI) is a devastating complication of joint arthroplasty surgery typified by biofilm formation. Currently, mechanisms whereby biofilms persist and evade immune-mediated clearance in immune competent patients remain largely ill-defined. Therefore, the current study characterized leukocyte infiltrates and inflammatory mediator expression in tissues from patients with PJI compared to aseptic loosening. CD33+HLA-DR-CD66b+CD14-/low granulocytic myeloid-derived suppressor cells (G-MDSCs) were the predominant leukocyte population at sites of human PJI compared to aseptic tissues. MDSCs inhibit T cell proliferation, which coincided with reduced T cells in PJIs compared to aseptic tissues. IL-10, IL-6, and CXCL1 were significantly elevated in PJI tissues and have been implicated in MDSC inhibitory activity, expansion, and recruitment, respectively, which may account for their preferential increase in PJIs. This bias towards G-MDSC accumulation during human PJI could account for the chronicity of these infections by preventing the pro-inflammatory, antimicrobial actions of immune effector cells. Clinical Significance: Animal models of PJI have revealed a critical role for MDSCs and IL-10 in promoting infection persistence; however, whether this population is prevalent during human PJI and across distinct bacterial pathogens remains unknown. This study has identified that granulocytic-MDSC infiltrates are unique to human PJIs caused by distinct bacteria, which are not associated with aseptic loosening of prosthetic joints. Better defining the immune status of human PJIs could lead to novel immune-mediated approaches to facilitate PJI clearance in combination with conventional antibiotics. This article is protected by copyright. All rights reserved |
| Databáze: | OpenAIRE |
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