Modulation of host cell pathways by <i>Coxiella burnetii</i> Dot/Icm effectors

<i>Coxiella burnetii</i>, the etiological agent of Q fever, is a significant intracellular bacterial pathogen. <i>C. burnetii</i> is a highly infectious pathogen that primarily targets pulmonary alveolar macrophages during natural infection. It can then disseminate to macrophages in other tissues and organs, leading to chronic infections. <i>C. burnetii</i> is capable of infecting a variety of cultured cells, including primary macrophages, macrophage-like cells, epithelial cells, and fibroblasts. The virulence of <i>C. burnetii</i> is entirely dependent on the Dot/Icm type IVB secretion system (T4BSS), which delivers effectors into infected cells to modulate cellular pathways for the biogenesis of the Coxiella-containing vacuole that supports its intracellular replication. A deeper understanding of how <i>C</i>. <i>burnetii</i> exploits host cell processes is essential for developing novel therapeutic strategies to combat infections caused by this important pathogen. This review summarizes the historical milestones and recent advances in our understanding of the structure and function of the <i>C. burnetii</i> Dot/Icm system and its effectors.