Li Sumeng, Li Shiqi, Cheng Yi, Liu Jing, Jia Hang, Xiang Tiandan, Shu Yiwen, Du Yanqin, Wang Xiaoyan, Xu Ling, Zheng Zhong, Liu Yanan, Wu Jun, Zheng Xin
Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Joint International Laboratory of Infection and Immunity, Huazhong University of Science and Technology, Wuhan, China.
J Med Virol. 2025 Aug;97(8):e70516. doi: 10.1002/jmv.70516.
Hepatitis B virus (HBV) and bacterial infections are major global health concerns. However, the impact of bacterial co-infection on HBV clearance remains unclear. To investigate how bacterial co-infection affects HBV clearance, we used a mouse model with chronic HBV replication and Klebsiella pneumoniae co-infection. We evaluated HBV virological markers, innate immune responses, inflammation, and intrahepatic HBV-specific T cell responses, with and without antibiotic treatment or MDSCs depletion. Our findings demonstrate that bacterial co-infection activates innate immunity and inflammation in the liver, leading to initial activation followed by exhaustion of HBV-specific CD4 and CD8 T cells, which delays HBV clearance. Antibiotic treatment alleviated inflammation and restored HBV elimination, while MDSCs depletion exacerbated inflammation and induced premature exhaustion of HBV-specific T cells. These results suggest that bacterial co-infection disrupts HBV-specific T cell responses and impairs HBV clearance, with MDSCs playing an indispensable role in indirectly regulating T cell activation, primarily through modulating the innate immune response and inflammatory pathways.
乙型肝炎病毒（HBV）和细菌感染是全球主要的健康问题。然而，细菌合并感染对HBV清除的影响仍不清楚。为了研究细菌合并感染如何影响HBV清除，我们使用了慢性HBV复制和肺炎克雷伯菌合并感染的小鼠模型。我们评估了有无抗生素治疗或MDSCs清除情况下的HBV病毒学标志物、固有免疫反应、炎症以及肝内HBV特异性T细胞反应。我们的研究结果表明，细菌合并感染激活肝脏中的固有免疫和炎症，导致HBV特异性CD4和CD8 T细胞最初激活，随后耗竭，从而延迟HBV清除。抗生素治疗减轻了炎症并恢复了HBV清除，而MDSCs清除加剧了炎症并诱导HBV特异性T细胞过早耗竭。这些结果表明，细菌合并感染破坏HBV特异性T细胞反应并损害HBV清除，MDSCs在间接调节T细胞激活中发挥不可或缺的作用，主要是通过调节固有免疫反应和炎症途径。
