PD-1/PD-L1 blockade is a potent adjuvant in treatment of Staphylococcus aureus osteomyelitis in mice

被引：31

作者：

Li, Kaiqun ^{[1
,2
]}

Chen, Yuhui ^{[1
,2
]}

Lin, Yihuang ^{[1
,2
]}

Zhang, Guangyan ^{[1
,2
]}

Su, Jianwen ^{[1
,2
]}

Wu, Xiaohu ^{[1
,2
]}

Cheng, Caiyu ^{[1
,2
]}

Wang, Yutian ^{[1
,2
]}

Yu, Bin ^{[1
,2
,3
]}

Zhang, Xianrong ^{[1
,2
,3
]}

机构：

[1] Southern Med Univ, Nanfang Hosp, Dept Orthoped, Div Orthoped & Traumatol, 1838 North Guangzhou Ave, Guangzhou 510515, Guangdong, Peoples R China

[2] Southern Med Univ, Nanfang Hosp, Guangdong Prov Key Lab Bone & Cartilage Regenerat, 1838 North Guangzhou Ave, Guangzhou 510515, Guangdong, Peoples R China

[3] Southern Med Univ, Nanfang Hosp, Dept Orthoped, Div Orthoped & Traumatol, 1838 North Guangzhou Ave, Guangzhou 510515, Guangdong, Peoples R China

来源：

MOLECULAR THERAPY | 2023年 / 31卷 / 01期

基金：

国家自然科学基金重大项目; 中国国家自然科学基金;

关键词：

PD-1; EXPRESSION;

D O I：

10.1016/j.ymthe.2022.09.006

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

There is no effective therapy for implant-associated Staphylo-coccus aureus osteomyelitis, a devastating complication after orthopedic surgery. An immune-suppressive profile with up -regulated programmed cell death 1/programmed death ligand 1 (PD-1/PD-L1) was identified based on our transcriptional data (GEO: GSE166522) from a mouse model of S. aureus osteomyelitis. PD-1/PD-L1 expression was up-regulated mainly in F4/80+ macrophages surrounding the abscess in S. aureus-infected bone. Mechanistically, PD-1/PD-L1 acti-vated mitophagy to suppress production of mitochondrial reactive oxygen species (ROS), suppressing the bactericidal function of macrophages. Using neutralizing antibodies for PD-L1 or PD-1, or knockout of PD-L1 adjuvant to genta-micin markedly reduced mitophagy in bone marrow F4/80+ cells, enhanced bacterial clearance in bone tissue and im-plants, and reduced bone destruction in mice. PD-1/PD-L1 expression was also increased in the bone marrow from indi-viduals with S. aureus osteomyelitis. These findings uncover a so far unknown function of PD-1/PD-L1-mediated mitophagy in suppressing the bactericidal function of bone marrow mac-rophages.

引用

页码：174 / 192

页数：19

共 41 条

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