Autoinducer-2 of Fusobacterium nucleatum promotes macrophage M1 polarization via TNFSF9/IL-1β signaling

The effect of Fusobacterium nucleatum (F. nucleatum) autoinducer-2 (AI-2) on the polarization of macrophages and the underlying mechanism is not known. We investigated the effect of F. nucleatum AI-2 on the migration and polarization of cultured macrophages. We further screened AI-2-interacting proteins in macrophages using a quantitative proteomics strategy, and evaluated the expression of TNFSF9/TRAF1/p-AKT/IL-1β signaling in cultured macrophages and human colorectal cancer (CRC). The data showed that F. nucleatum AI-2 enhanced the mobility and M1 polarization of macrophages, possibly through TNFSF9/TRAF1/p-AKT/IL-1β signaling. Moreover, TNFSF9 and IL-1β expression was significantly increased in human CRCs when compared to normal colon (P < 0.05), and was associated with AI-2 concentration and increased survival. Together, our data suggested that AI-2 induced macrophage M1 polarization by activating the TNFSF9/IL-1β pathway. Thus, AI-2 may serve as a promising novel target for immunotherapy of gut microbiota-related diseases.