We speculate that the Brucella T4SS effector protein BspF has the potential to alter the modification of intracellular proteins, thereby affecting intracellular Hippo signaling pathway, thus promoting the reproduction of Brucella. Hippo signaling pathway is also a part of immune response, which may also be associated with chronically low immunity in patients with brucellosis. This evidence concerns the gene PROS1 and brucellosis.