Yersinia pestis Interacts With SIGNR1 (CD209b) for Promoting Host Dissemination and Infection

Abstract

<i>Yersinia pestis</i>, a Gram-negative bacterium and the etiologic agent of plague, has evolved from <i>Yersinia pseudotuberculosis</i>, a cause of a mild enteric disease. However, the molecular and biological mechanisms of how <i>Y. pseudotuberculosis</i> evolved to such a remarkably virulent pathogen, <i>Y. pestis</i>, are not clear. The ability to initiate a rapid bacterial dissemination is a characteristic hallmark of <i>Y. pestis</i> infection. A distinguishing characteristic between the two <i>Yersinia</i> species is that <i>Y. pseudotuberculosis</i> strains possess an O-antigen of lipopolysaccharide (LPS) while <i>Y. pestis</i> has lost the O-antigen during evolution and therefore exposes its core LPS. In this study, we showed that <i>Y. pestis</i> utilizes its core LPS to interact with SIGNR1 (CD209b), a C-type lectin receptor on antigen presenting cells (APCs), leading to bacterial dissemination to lymph nodes, spleen and liver, and the initiation of a systemic infection. We therefore propose that the loss of O-antigen represents a critical step in the evolution of <i>Y. pseudotuberculosis</i> into <i>Y. pestis</i> in terms of hijacking APCs, promoting bacterial dissemination and causing the plague.