PMID- 28813499 OWN - NLM STAT- MEDLINE DCOM- 20171013 LR - 20240326 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 12 IP - 8 DP - 2017 TI - Staphylococcus aureus biofilm elicits the expansion, activation and polarization of myeloid-derived suppressor cells in vivo and in vitro. PG - e0183271 LID - 10.1371/journal.pone.0183271 [doi] LID - e0183271 AB - 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. FAU - Peng, Kuo-Ti AU - Peng KT AD - Department of Orthopedic Surgery, Chang Gung Memorial Hospital, Chiayi, Taiwan. FAU - Hsieh, Ching-Chuan AU - Hsieh CC AD - Department of Surgery, Chang Gung Memorial Hospital, Chiayi, Taiwan. FAU - Huang, Tsung-Yu AU - Huang TY AD - Division of Infection Disease, Department of Internal Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan. AD - Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan. FAU - Chen, Pei-Chun AU - Chen PC AD - Department of Orthopedic Surgery, Chang Gung Memorial Hospital, Chiayi, Taiwan. FAU - Shih, Hsin-Nung AU - Shih HN AD - Department of Orthopedic Surgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan. FAU - Lee, Mel S AU - Lee MS AD - Department of Orthopedic Surgery, Chang Gung Memorial Hospital, Kaohsiung, Taiwan. FAU - Chang, Pey-Jium AU - Chang PJ AUID- ORCID: 0000-0002-6492-0346 AD - Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan. AD - Department of Nephrology, Chang-Gung Memorial Hospital, Chiayi, Taiwan. LA - eng PT - Journal Article DEP - 20170816 PL - United States TA - PLoS One JT - PloS one JID - 101285081 SB - IM MH - Animals MH - Biofilms/*growth & development MH - Cells, Cultured MH - Flow Cytometry MH - Macrophages/metabolism MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Microscopy, Confocal MH - Microscopy, Electron, Scanning MH - Myeloid Cells/*cytology MH - Rats MH - Reverse Transcriptase Polymerase Chain Reaction MH - Staphylococcus aureus/*physiology MH - T-Lymphocytes/metabolism MH - T-Lymphocytes, Regulatory/metabolism PMC - PMC5559065 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2017/08/17 06:00 MHDA- 2017/10/14 06:00 PMCR- 2017/08/16 CRDT- 2017/08/17 06:00 PHST- 2017/05/07 00:00 [received] PHST- 2017/08/01 00:00 [accepted] PHST- 2017/08/17 06:00 [entrez] PHST- 2017/08/17 06:00 [pubmed] PHST- 2017/10/14 06:00 [medline] PHST- 2017/08/16 00:00 [pmc-release] AID - PONE-D-17-17582 [pii] AID - 10.1371/journal.pone.0183271 [doi] PST - epublish SO - PLoS One. 2017 Aug 16;12(8):e0183271. doi: 10.1371/journal.pone.0183271. eCollection 2017.