Abstract:Brucella is a genus of globally widespread zoonotic pathogens capable of infecting wild animals, domestic animals, and humans. To establish and sustain chronic infections within the host, Brucella have evolved multiple strategies to evade host immune responses and extensively replicate in host cells, which primarily rely on the type Ⅳ secretion system (T4SS) and its secreted effectors. The T4SS functions by directly injecting effectors into host cells, modulating various host cell functions to help the pathogen evade immune surveillance, manipulate the intracellular environment, and promote its survival and replication. This article reviews the structure and function of the Brucella T4SS and the latest research progress in the role of Brucella T4SS effectors in regulating host cell functions, exploring how bacteria of Brucella manipulate host cell signaling pathways to control intracellular vacuole dynamics and establish a replicative niche conducive to bacterial survival. These advancements provide new insights into the pathogenesis of Brucella infections and aid in the development of more effective strategies for preventing and treating Brucella-related diseases.