STING/Type I Interferon Pathway Activation Confers Multimodal Therapeutic Benefits in Osteomyelitis
Yang Chen, Jianhua Lv, Yuanqing Cai, Xuhui Yuan, Hongxin Hu, Jiayu Li, Yiming Lin, Hongyan Li, Lan Lin, Huangfeng Lin, Chaofan Zhang, Qijin Wang, Ying Huang, Zida Huang, Wenbo Li, Susheng Niu, Jianhua Lin, Bin Yang, Xinyu Fang, Wenming ZhangABSTRACT
Osteomyelitis is an inflammatory bone disease caused by pathogenic microorganisms and characterized by severe pain, extensive bone destruction, and reduced antibiotic efficacy due to local abscess formation. This study investigates the therapeutic potential of activating the STING (stimulator of interferon genes) pathway in osteomyelitis. In murine femoral osteomyelitis models induced by Staphylococcus aureus ( S. aureus ), STING agonists alleviate osteomyelitis‐associated pain, suppress infection‐induced bone destruction, and reduce local abscess formation. These effects depend on host STING/type I interferon (IFN‐I) signaling and involve three mechanisms: inhibition of nociceptor activation by pathogens, suppression of osteoclast differentiation and function without affecting osteoblast activity, and downregulation of interleukin‐1β (IL‐1β), leading to reduced neutrophil recruitment and abscess formation. By reducing abscess formation as a physical barrier, STING agonists enhance the antibacterial efficacy of conventional antibiotics such as vancomycin at the site of infection. In summary, these findings suggest that the synergistic mechanisms activated by STING represent a promising therapeutic target for alleviating pain and improving clinical outcomes in osteomyelitis.