Human prosthetic joint infections are associated with myeloid-derived suppressor cells (MDSCs): Implications for infection persistence

Cortney E. Heim, Debbie Vidlak, Jessica Odvody, Curtis W. Hartman, Kevin L. Garvin, Tammy Kielian

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1605-1613
Number of pages9
JournalJournal of Orthopaedic Research
Volume36
Issue number6
DOIs
StatePublished - Jun 2018

Keywords

  • biofilm
  • myeloid-derived suppressor cells
  • neutrophils
  • prosthetic joint infection
  • staphylococci

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine

Fingerprint Dive into the research topics of 'Human prosthetic joint infections are associated with myeloid-derived suppressor cells (MDSCs): Implications for infection persistence'. Together they form a unique fingerprint.

  • Cite this