Staphylococcus aureus biofilm elicits the expansion, activation and polarization of myeloid-derived suppressor cells in vivo and in vitro.

Kuo-Ti Peng,Ching-Chuan Hsieh,Tsung-Yu Huang,Hsin-Nung Shih,Pei-Chun Chen,Pey-Jium Chang,Mel S Lee,Claudio Tripodo

doi:10.1371/journal.pone.0183271

Abstract

Staphylococcus aureus (S. aureus) is one of the most common causes of biofilm infections in periprosthetic joint infections (PJIs). Accumulating evidence has shown that the immunosuppressive environment established by S. aureus biofilm infection in PJIs involves the presence of myeloid-derived suppressor cells (MDSCs) and M2-macrophages. Due to the diversity of MDSCs, little is known about whether S. aureus biofilm preferentially expands specific MDSC subsets or whether MDSCs can further differentiate into M2-macrophages during S. aureus biofilm infection. Here, we show that in agreement with the results from an established rat PJI model, S. aureus biofilm cocultured with freshly isolated bone marrow cells (BMCs) in vitro significantly increases the proportions of MDSCs, total macrophages and M2-macrophages. Interestingly, we find that treatment of the BMCs in vitro with S. aureus biofilm preferentially promotes the expansion of monocytic MDSCs but not granulocytic MDSCs. Biofilm treatment also substantially enhances the overall MDSC immunosuppressive activity in addition to the MDSC expansion in vitro. Importantly, we provide evidence that S. aureus biofilm is capable of further stimulating the conversion of monocytic MDSCs into M2-macrophages in vitro and in vivo. Collectively, our studies reveal a direct link between MDSCs and M2-macrophages occurring in S. aureus-associated PJIs.

Highlights

Prosthetic joint infections (PJIs) are a devastating complication after arthroplasty, which greatly affect the quality of a patient’s recovery [1,2,3]
These results indicated that our established PJI model in rats shows persistent biofilm infection and may allow further investigation of host immune responses to S. aureus biofilm infection in vivo
To investigate the possible immunosuppressive effect caused by S. aureus biofilm infection in vivo, we examined if the proportions of the circulating myeloid-derived suppressor cells (MDSCs), total macrophages and M2-macrophages were changed during S. aureus infection in our PJI model

Summary

Introduction

Prosthetic joint infections (PJIs) are a devastating complication after arthroplasty, which greatly affect the quality of a patient’s recovery [1,2,3]. Activation and polarization of MDSCs by Staphylococcus aureus biofilm arthroplasty [4]. Staphylococcus aureus (S. aureus), a Gram-positive microorganism, is a major human pathogen and a major cause of community-associated and nosocomial infections. It elicits biofilm infection on orthopedic implants or other internal medical devices. S. aureus biofilm infection in PJIs often causes a serious health care concern based on their protection from antibiotic treatment and the host’s immune system. The methicillin-resistant S. aureus (MRSA) has gradually increased its presence in the human population causing this pathogen as a greater therapeutic problem [8]. The development of vaccines or immunotherapies to treat S. aureusassociated biofilm infection is an urgent need in the realm of public health [9, 10]

Methods

Results

Conclusion