Phagocyte-targeted Effects of Yersinia pseudotuberculosis Proteins and Their Role in Bacterial Colonization of the Liver

Yersinia pseudotuberculosis (Yptb) causes intestinal infection and can spread to the liver, where the bacterium induces hemosiderosis, abscesses, and hepatitis. To evade the immune response of the host organism, Yptb expresses at least six plasmid-encoded Yersinia outer proteins belonging to the Type III secretion system, which suppress phagocytic activity. Recently, evidence has accumulated that chromosome-encoded protein toxins are also involved in the anti-phagocytic defense of Yptb. Most of these toxins have been found in isolates from patients with Far East scarlet-like fever, often accompanied by liver pathology. Yersinia proteins contribute to bacterial colonization of lymphoid organs through their effects on immune cells. A thorough understanding of the immunomodulatory effects of these toxic proteins on bacterial dissemination and colonization in the liver will contribute to the development of novel approaches to cure hepatic pathology during Yptb infection. The review aimed to summarize the current data on the mechanisms of effects of Yptb plasmid- and chromosome-encoded toxins on bacterial colonization in the liver. The review highlights the fine-tuning of immune system activity by toxins encoded by both a 70-kb plasmid and chromosomes, through various mechanisms of action of individual proteins and their interactions. The focus is on mechanisms that promote bacterial survival in macrophages, including those that facilitate bacterial-induced macrophage polarization towards the M2 phenotype. The role of a type of phagocyte death in bacterial dissemination and colonization in the organs is also discussed.