Yersinia pseudotuberculosisExploits CD209 Receptors for Promoting Host Dissemination and Infection

Abstract

Yersinia pseudotuberculosis is a Gram-negative enteropathogen and causes gastrointestinal infections. It disseminates from gut to mesenteric lymph nodes (MLNs), spleen, and liver of infected humans and animals. Although the molecular mechanisms for dissemination and infection are unclear, many Gram-negative enteropathogens presumably invade the small intestine via Peyer's patches to initiate dissemination. In this study, we demonstrate that Y. pseudotuberculosis utilizes its lipopolysaccharide (LPS) core to interact with CD209 receptors, leading to invasion of human dendritic cells (DCs) and murine macrophages. These Y. pseudotuberculosis-CD209 interactions result in bacterial dissemination to MLNs, spleens, and livers of both wild-type and Peyer's patchdeficient mice. The blocking of the Y. pseudotuberculosis-CD209 interactions by expression of O-antigen and with oligosaccharides reduces infectivity. Based on the well-documented studies in which HIV-CD209 interaction leads to viral dissemination, we therefore propose an infection route for Y. pseudotuberculosis where this pathogen, after penetrating the intestinal mucosal membrane, hijacks the Y. pseudotuberculosis-CD209 interaction antigen-presenting cells to reach their target destinations, MLNs, spleens, and livers.

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

“…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).…”

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

“…Previous results, including some of our work, showed that APCs such as macrophages and dendritic cells (DCs) express CD209 receptors on their surface and have been shown to interact with pathogens that target CD209s for invasion (22,24,25,28,34,36,(54)(55)(56). To determine whether T. gondii can interact with mouse macrophages more readily, we examined the ability of T. gondii to invade peritoneal macrophages that express CD209 (57,58) compared to a macrophage cell line (RAW 264.7) that lacks the expression of CD209 receptors on its surface (59).…”

“…It is well-documented that the surfaces of most parasites are highly glycosylated (11,27,29,76). Further investigations need to be done to determine corresponding parasite ligands, as we did in identification of the carbohydrate LPS core from many Gram-negative bacteria (29,30,38,40,56,59); as well as immune responses elicited by the T. gondii. Moreover, HIV uses gp120-DCSIGN interaction to initiate capture by DCs and transmission to CD4+ T cells (19).…”

“…To support the speculations shown in Figure 1, we tested the ability of T. gondii to invade CHO cells and CD209a (CHO-hDC-SIGN) and CD209b (CHO-m-SIGN-R1)-expressing CHO cells. We have been using the cell lines for many of our previous and current studies (27,29,30,56,59). Figure 2A shows that there was increased invasion and fluorescence in CHO-h-DC-SIGN than in CHO.…”

“…Mannan was the most commonly used inhibitor in our study since it was possibly more specific (56,60). Mannan's inhibitory effect was therefore further tested at different concentrations to determine its efficacy even at low doses.…”