Fusobacterium nucleatum aggravates rheumatoid arthritis through FadA-containing outer membrane vesicles

作者：Hong, Mukeng; Li, Zhuang; Liu, Haihua; Zheng, Songyuan; Zhang, Fangling; Zhu, Junqing; Shi, Hao; Ye, Haixing; Chou, Zhantu; Gao, Lei; Diao, Jianxin; Zhang, Yang; Zhang, Dongxin; Chen, Shixian^*; Zhou, Hongwei^*; Li, Juan^*

来源：Cell Host and Microbe, 2023, 31(5): 798-+.

DOI：10.1016/j.chom.2023.03.018

• ARYL-HYDROCARBON RECEPTOR
• MACROPHAGES

Rheumatoid arthritis (RA) is an autoimmune disorder that has been associated with the gut microbiota. However, whether and how the gut microbiota plays a pathogenic role in RA remains unexplored. Here, we observed that Fusobacterium nucleatum is enriched in RA patients and positively associated with RA severity. F. nucleatum similarly aggravates arthritis in a mouse model of collagen-induced arthritis (CIA). F. nucleatum outer membrane vesicles (OMVs) containing the virulence determinant FadA translo-cate into the joints, triggering local inflammatory responses. Specifically, FadA acts on synovial macro-phages, resulting in the activation of the Rab5a GTPase involved in vesicle trafficking and inflammatory pathways and YB-1, a key regulator of inflammatory mediators. OMVs containing FadA and heightened Rab5a-YB-1 expression were observed in RA patients compared with controls. These findings suggest a causal role of F. nucleatum in aggravating RA and provide promising therapeutic targets for clinically ameliorating RA.

• 单位
  南方医科大学