Interactions of Bacterial Toxin CNF1 and Host JAK1/2 Driven by Liquid-Liquid Phase Separation Enhance Macrophage Polarization
Xuan Sun, Jianming Yang, Xueqin Deng, Yuting Wei, Changying Wang, Yaxiu Guo, Huan Yang, Liu Yang, Chunhui Miao, Junqiang Lv, Yawen Xiao, Hong Zhang, Zhi Yao, Quan Wang
Abstract
CNF1 is a key toxin secreted by UPEC, which induces inflammation during UPEC infections. CNF1 is well known to activate Rho GTPases to disturb host cell signaling pathways. Macrophage reprogramming plays important roles in inflammation; however, the effect of CNF1 on macrophage polarization is not reported. This study demonstrated the role and mechanism of CNF1 in promoting M1 macrophage polarization during UPEC-induced acute kidney infections. Importantly, we identified Rho GTPase-independent effect of CNF1 as an adaptor on interfering with host cell signals and demonstrated that CNF1 exhibited LLPS to drive its interaction with host proteins, which improve our understanding of the UPEC-host interactions and UTI pathogenesis.