State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin University, Changchun, China.
Institute of Microbiology Department, Jilin Provincial Center for Disease Control and Prevention, Changchun, China.
Front Immunol. 2024 Oct 21;15:1466520. doi: 10.3389/fimmu.2024.1466520. eCollection 2024.
() is a zoonotic bacterial pathogen that causes chronic host infections. The eradication of brucellosis using antibiotic therapy is often incomplete or slow. In a mouse model, the predominance of alternatively activated macrophages (also known as M2) plays an essential role in sustaining chronic infection. The underlying functional mechanism by which M2 sustains chronic infection remains unclear. Here, we show that can enter M2 via triggering receptor expressed on myeloid cells 2 (TREM2) and promotes the upregulation of TREM2 expression of M2 in a type IV secretion system (T4SS)-dependent manner. Increased TREM2 enhances growth within M2 by suppressing intracellular ROS production, preventing M2 pyroptosis via suppression of mitochondrial ROS (mROS), and promoting M2 proliferation by increasing β-catenin expression. In line with these results, downregulation of TREM2 expression suppressed intracellular growth and M2 proliferation and induced M2 pyroptosis. In our mouse model, upregulation of TREM2 expression sustained the accumulation of M2 and chronic infection, whereas downregulation of TREM2 expression restricted M2 proliferation and chronic infection. Collectively, our results suggest that targeting TREM2 may be a potential adjunct to antibiotic therapy for the prevention of chronic infection.
布鲁氏菌是一种人畜共患的细菌病原体，可引起慢性宿主感染。抗生素治疗根除布鲁氏菌病往往不完全或缓慢。在小鼠模型中，交替激活的巨噬细胞（也称为 M2）的优势在维持慢性感染中起着至关重要的作用。M2 维持慢性感染的潜在功能机制尚不清楚。在这里，我们表明，布鲁氏菌可以通过触发髓样细胞表达的受体 2（TREM2）进入 M2，并通过 IV 型分泌系统（T4SS）依赖性方式促进 M2 中 TREM2 的上调。增加的 TREM2 通过抑制细胞内 ROS 产生来增强 M2 内的生长，通过抑制线粒体 ROS（mROS）防止 M2 细胞焦亡，并通过增加 β-连环蛋白表达来促进 M2 增殖。与这些结果一致，下调 TREM2 表达抑制了布鲁氏菌的细胞内生长和 M2 的增殖，并诱导了 M2 细胞焦亡。在我们的小鼠模型中，上调 TREM2 表达维持了 M2 和布鲁氏菌慢性感染的积累，而下调 TREM2 表达限制了 M2 的增殖和慢性感染。总的来说，我们的结果表明，靶向 TREM2 可能是抗生素治疗预防慢性布鲁氏菌感染的潜在辅助手段。
