TANK-binding Kinase 1 regulates the intracellular survival of Brucella.

Brucella, the causative agent of brucellosis, is a globally important intracellular pathogen. TANK-binding kinase 1 (TBK1), a key component of the type I interferon induction pathway, is known to play a critical role in controlling intracellular bacterial infections. However, the function of TBK1 during Brucella infection remains poorly understood. In this study, we investigated the role of TBK1during Brucella infection. We observed that Brucella infection upregulates TBK1 expression in macrophages. Using TBK1-targeting small interfering RNAs (siRNAs) and overexpression approaches, we examined how TBK1 regulates the intracellular survival of Brucella. Results demonstrated that TBK1 knockdown significantly promoted intracellular bacterial growth and reduced the production of the pro-inflammatory cytokines IL-1β, IL-6, TNF-α, and IFN-γ. Conversely, TBK1 overexpression inhibited intracellular Brucella growth and enhanced the secretion of these cytokines. Moreover, Brucella infection also stimulated TBK1 expression in mice, and TBK1 knockout promoted bacterial survival in vivo. Furthermore, during Brucella infection, TBK1 inhibition significantly suppressed NF-κB activity, whereas TBK1 overexpression enhanced it. Collectively, our findings demonstrated that TBK1 acts as an essential regulator of Brucella survival and growth both in vitro and in vivo. The mechanism by which TBK1 induces pro-inflammatory cytokines and activates NF-κB warrants further investigation to elucidate its role in bacterial intracellular persistence.