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

Cell host & microbe 2023 May 10

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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 translocate into the joints, triggering local inflammatory responses. Specifically, FadA acts on synovial macrophages, 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. Copyright © 2023 Elsevier Inc. All rights reserved.

Citation

Mukeng Hong, Zhuang Li, Haihua Liu, Songyuan Zheng, Fangling Zhang, Junqing Zhu, Hao Shi, Haixing Ye, Zhantu Chou, Lei Gao, Jianxin Diao, Yang Zhang, Dongxin Zhang, Shixian Chen, Hongwei Zhou, Juan Li. Fusobacterium nucleatum aggravates rheumatoid arthritis through FadA-containing outer membrane vesicles. Cell host & microbe. 2023 May 10;31(5):798-810.e7