TY - JOUR
T1 - Interleukin-10 production by myeloid-derived suppressor cells contributes to bacterial persistence during staphylococcus aureus orthopedic biofilm infection
AU - Heim, Cortney E.
AU - Vidlak, Debbie
AU - Kielian, Tammy
PY - 2015/11
Y1 - 2015/11
N2 - 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.
AB - 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.
KW - IL-10
KW - MDSC
KW - Macrophage
UR - http://www.scopus.com/inward/record.url?scp=84948951226&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84948951226&partnerID=8YFLogxK
U2 - 10.1189/jlb.4VMA0315-125RR
DO - 10.1189/jlb.4VMA0315-125RR
M3 - Article
C2 - 26232453
AN - SCOPUS:84948951226
VL - 98
SP - 1003
EP - 1013
JO - Journal of Leukocyte Biology
JF - Journal of Leukocyte Biology
SN - 0741-5400
IS - 6
ER -