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

Abstract

Yersinia pestis, a Gram-negative bacterium and the etiologic agent of plague, has evolved from Yersinia pseudotuberculosis, a cause of a mild enteric disease. However, the molecular and biological mechanisms of how Y. pseudotuberculosis evolved to such a remarkably virulent pathogen, Y. pestis, are not clear. The ability to initiate a rapid bacterial dissemination is a characteristic hallmark of Y. pestis infection. A distinguishing characteristic between the two Yersinia species is that Y. pseudotuberculosis strains possess an O-antigen of lipopolysaccharide (LPS) while Y. pestis has lost the O-antigen during evolution and therefore exposes its core LPS. In this study, we showed that Y. pestis 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 Y. pseudotuberculosis into Y. pestis in terms of hijacking APCs, promoting bacterial dissemination and causing the plague.

CD209 C-Type Lectins Promote Host Invasion, Dissemination, and Infection of Toxoplasma gondii

“…(14,41,(61)(62)(63)(64)(65). Studies have shown that pathogens such as viral HIV and bacterial Y. pestis were able to bind CD209 to hijack APCs as the Trojan horses for host dissemination (19,42,44). In this study, our results suggested that T. gondii may use the similar mechanisms for its host dissemination.…”

“…APCs express at least three immunoreceptors that belong to the calcium-dependent (Ctype) lectin family: DC-specific intercellular adhesion molecule 3 grabbing non integrin (DC-SIGN, CD209), DEC-205 (CD205), and Langerin (CD207), which can be utilized by pathogens to initiate infection (20,(38)(39)(40). For example, studies indicated that several microbial pathogens like HIV and bacterial Yersinia pestis, the etiologic agent of plague, were able to interact with CD209s in order to hijack APCs as the Trojan horses (41) to promote host dissemination (19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(42)(43)(44). However, there were few such examples for studies on parasites.…”

Salmonella enterica Serovar Typhimurium Interacts with CD209 Receptors To Promote Host Dissemination and Infection

“…As a result, after entering the skin via an infected flea, Y. pestis, with its LPS core, can directly interact with APCs, leading to phagocytosis of the pathogen (26). As reported in our recent publication (11), the infected APCs consequently serve as "taxis" to deliver Y. pestis to the lymph nodes and initiate plague infection (39).…”

“…ST-pAY100.1 is S. Typhimurium LT2 transformed with the plasmid pAY100.1 (the cloning vector pBR322 carrying the O-antigen operon of Y. enterocolitica O:3) (25). Previous studies showed that the expression of this O-antigen blocks the interactions between the LPS core and CD209s (11,12,26).…”

“…Two very recent studies further showed that using the LPS core, Yersinia spp. may interact with CD209s to promote host dissemination and infection (11,12).…”