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

Journal of Leukocyte Biology

Cortney E. Heim¹  Debbie Vidlak¹  Tammy Kielian¹ 

[1] Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska, USADepartment of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska, USADepartment of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska, USA

关键词: MDSC;    IL-10;    macrophage;   

DOI  :  10.1189/jlb.4VMA0315-125RR

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

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 immune-mediated 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 wild-type 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 biofilm-infected tissues. These results demonstrate that interleukin-10 production by myeloid-derived suppressor cells contributes to the persistence of S. aureus orthopedic biofilm infections.

【 授权许可】

Unknown