Modulation of innate immune signaling by a <i>Coxiella burnetii</i> eukaryotic-like effector protein
Mélanie Burette, Julie Allombert, Karine Lambou, Ghizlane Maarifi, Sébastien Nisole, Elizabeth Di Russo Case, Fabien P. Blanchet, Cédric Hassen‐Khodja, Stéphanie Cabantous, James E. Samuel, Eric Martínez, Matteo Bonazzi
Abstract
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.