Interleukin-10 production by myeloid-derived suppressor cells contributes to bacterial persistence during staphylococcus aureus orthopedic biofilm infection

Cortney E. Heim, Debbie Vidlak, Tammy Kielian

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

Staphylococcus aureus is known to establish biofilms on medical devices. We recently demonstrated that Ly6GhighLy6C+ myeloid-derived suppressor cells are critical for allowing S. aureus biofilms to subvert immunemediated clearance; however, the mechanisms whereby myeloid-derived suppressor cells promote biofilm persistence remain unknown. Interleukin-10 expression was significantly increased in a mouse model of S. aureus orthopedic implant biofilm infection with kinetics that mirrored myeloid-derived suppressor cell recruitment. Because myeloid-derived suppressor cells produce interleukin-10, we explored whether it was involved in orchestrating the nonproductive immune response that facilitates biofilm formation. Analysis of interleukin-10–green fluorescent protein reporter mice revealed that Ly6GhighLy6C+ myeloid-derived suppressor cells were the main source of interleukin-10 during the first 2 wk of biofilm infection, whereas monocytes had negligible interleukin-10 expression until day 14. Myeloid-derived suppressor cell influx into implant-associated tissues was significantly reduced in interleukin-10 knockout mice at day 14 postinfection, concomitant with increased monocyte and macrophage infiltrates that displayed enhanced proinflammatory gene expression. Reduced myeloid-derived suppressor cell recruitment facilitated bacterial clearance, as revealed by significant decreases in S. aureus burdens in the knee joint, surrounding soft tissue, and femur of interleukin-10 knockout mice. Adoptive transfer of interleukin-10 wildtype myeloid-derived suppressor cells into S. aureus–infected interleukin-10 knockout mice restored the local biofilm-permissive environment, as evidenced by increased bacterial burdens and inhibition of monocyte proinflammatory activity. These effects were both interleukin-10-dependent and interleukin-10-independent because myeloid-derived suppressor cell–derived interleukin-10 was required for promoting biofilm growth and anti-inflammatory gene expression in monocytes but was not involved in monocyte recruitment to biofilminfected tissues. These results demonstrate that interleukin-10 production by myeloid-derived suppressor cells contributes to the persistence of S. aureus orthopedic biofilm infections.

Original languageEnglish (US)
Pages (from-to)1003-1013
Number of pages11
JournalJournal of Leukocyte Biology
Volume98
Issue number6
DOIs
StatePublished - Nov 2015

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Keywords

  • IL-10
  • MDSC
  • Macrophage

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

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