Modulation of innate immune signaling by a Coxiella burnetii eukaryotic-like effector protein

Significance Coxiella burnetii is a stealth pathogen that evades innate immune recognition by inhibiting the NF-κB signaling pathway. This process is mediated by the bacterial Dot/Icm secretion system; however, the bacterial effector/s, as well as the molecular mechanism involved in this process have remained unknown to date. Here, by investigating C. burnetii proteins with eukaryotic-like features (EUGENs), we discovered a new effector protein, NopA (nucleolar protein A), which localizes at nucleoli of infected cells and perturbs nucleocytoplasmic transport by manipulating the intracellular gradients of the GTPase Ran. In doing so, NopA reduces the nuclear levels of transcription factors involved in the innate immune sensing of pathogens and single-handedly down-modulates the expression of a panel of cytokines.