TY - JOUR AU - Liang, Feihong AU - Guan, Huiting AU - Li, Wenhua AU - Zhang, Xue AU - Liu, Tingting AU - Liu, Yu AU - Mei, Jie AU - Jiang, Cheng AU - Zhang, Fengxue AU - Luo, Bangwei AU - Zhang, Zhiren PY - 2021 M3 - Original Research TI - Erythropoietin Promotes Infection Resolution and Lowers Antibiotic Requirements in E. coli- and S. aureus-Initiated Infections JO - Frontiers in Immunology UR - https://www.frontiersin.org/articles/10.3389/fimmu.2021.658715 VL - 12 SN - 1664-3224 N2 - Endogenous mechanisms underlying bacterial infection resolution are essential for the development of novel therapies for the treatment of inflammation caused by infection without unwanted side effects. Herein, we found that erythropoietin (EPO) promoted the resolution and enhanced antibiotic actions in Escherichia coli (E. coli)- and Staphylococcus aureus (S. aureus)-initiated infections. Levels of peritoneal EPO and macrophage erythropoietin receptor (EPOR) were elevated in self-limited E. coli-initiated peritonitis. Myeloid-specific EPOR-deficient mice exhibited an impaired inflammatory resolution and exogenous EPO enhanced this resolution in self-limited infections. Mechanistically, EPO increased macrophage clearance of bacteria via peroxisome proliferator-activated receptor γ (PPARγ)-induced CD36. Moreover, EPO ameliorated inflammation and increased the actions of ciprofloxacin and vancomycin in resolution-delayed E. coli- and S. aureus-initiated infections. Collectively, macrophage EPO signaling is temporally induced during infections. EPO is anti-phlogistic, increases engulfment, promotes infection resolution, and lowers antibiotic requirements. ER -