Role of the Yersinia pseudotuberculosis Virulence Plasmid in Pathogen-Phagocyte Interactions in Mesenteric Lymph Nodes.

Abstract

Yersinia pseudotuberculosis is an Enterobacteriaceae family member that is commonly transmitted by the fecal-oral route to cause infections. From the small intestine, Y. pseudotuberculosis can invade through Peyer's patches and lymph vessels to infect the mesenteric lymph nodes (MLNs). Infection of MLNs by Y. pseudotuberculosis results in the clinical presentation of mesenteric lymphadenitis. MLNs are important for immune responses to intestinal pathogens and microbiota in addition to their clinical relevance to Y. pseudotuberculosis infections. A characteristic of Y. pseudotuberculosis infection in MLNs is the formation of pyogranulomas. Pyogranulomas are composed of neutrophils, inflammatory monocytes, and lymphocytes surrounding extracellular microcolonies of Y. pseudotuberculosis. Key elements of the complex pathogen-host interaction in MLNs have been identified using mouse infection models. Y. pseudotuberculosis requires the virulence plasmid pYV to induce the formation of pyogranulomas in MLNs. The YadA adhesin and the Ysc-Yop type III secretion system (T3SS) are encoded on pYV. YadA mediates bacterial binding to host receptors, which engages the T3SS to preferentially translocate seven Yop effectors into phagocytes. The effectors promote pathogenesis by blocking innate immune defenses such as superoxide production, degranulation, and inflammasome activation, resulting in survival and growth of Y. pseudotuberculosis. On the other hand, certain effectors can trigger immune defenses in phagocytes. For example, YopJ triggers activation of caspase-8 and an apoptotic cell death response in monocytes within pyogranulomas that limits dissemination of Y. pseudotuberculosis from MLNs to the bloodstream. YopE can be processed as an antigen by phagocytes in MLNs, resulting in T and B cell responses to Y. pseudotuberculosis. Immune responses to Y. pseudotuberculosis in MLNs can also be detrimental to the host in the form of chronic lymphadenopathy. This review focuses on interactions between Y. pseudotuberculosis and phagocytes mediated by pYV that concurrently promote pathogenesis and host defense in MLNs. We propose that MLN pyogranulomas are immunological arenas in which opposing pYV-driven forces determine the outcome of infection in favor of the pathogen or host.