Host Langerin (CD207) is a receptor for Yersinia pestis phagocytosis and promotes dissemination

Abstract

Yersinia pestis is a Gram-negative bacterium that causes plague. After Y. pestis overcomes the skin barrier, it encounters antigen-presenting cells, such as Langerhans and dendritic cells. They transport the bacteria from the skin to the lymph nodes. However, the molecular mechanisms involved in bacterial transmission are unclear. Langerhans cells express Langerin (CD207), a calcium-dependent (C-type) lectin. Furthermore, Y. pestis possesses exposed core oligosaccharides. In this study, we show that Y. pestis invades Langerhans cells and Langerin-expressing transfectants. However, when the bacterial core oligosaccharides are shielded or truncated, Y. pestis propensity to invade Langerhans- and Langerin-expressing cells decreases. Moreover, the interaction of Y. pestis with Langerin-expressing transfectants is inhibited by purified Langerin, a DC-SIGN-like molecule, an anti-CD207 antibody, purified core oligosaccharides and several oligosaccharides. Furthermore, covering core oligosaccharides reduces the mortality associated with murine infection by adversely affecting the transmission of Y. pestis to lymph nodes. These results demonstrate that direct interaction of core oligosaccharides with Langerin facilitates the invasion of Langerhans cells by Y. pestis. Therefore, Langerin-mediated binding of Y. pestis to antigen-presenting cells may promote its dissemination and infection.

Yersinia versus host immunity: how a pathogen evades or triggers a protective response

“…Shortly after host entry, pathogenic yersiniae encounter an influx of immune cells, which they can either bypass or exploit to ensure survival and dissemination. Absence of the lipopolysaccharide (LPS) component O-antigen in Y. pestis is important for the invasion of dendritic cells expressing the C-type lectin Langerin [18]. Following inoculation into hind paws of mice, O-antigen-expressing derivatives are defective in spreading to sub-iliac lymph nodes, suggesting that exploitation of host Langerin is important for the efficient dissemination process associated with virulence in Y. pestis .…”

All the microbiology nematodes can teach us

“…But marine nematode lectins do not only provide a molecular basis to symbiosis specificity. They also testified how the study of naturally occurring nematodebacterium associations can help solving societal problems: recombinant Mermaid was indeed shown to block-among other pathogens (Zhang et al 2006(Zhang et al , 2008Mittal et al 2009;Yang et al 2015)-HIV-1 virus infection of human cells (Nabatov et al 2008).…”

Identification of host factors required for Yersinia pestis macrophage intracellular survival and their impact on vacuole maturation, acidification and trafficking.

“…In these studies KIM 10 pCD1 (-) strains were constructed with either a truncated outer core or O-polysaccharide covered core. Using these strains, in a fluorescence flow cytometry platform, they show the LPS core facilitates adherence to both dendritic and Langerhans cells, as mutants where the oligosaccharide core are truncated or covered by the O-polysaccharide are significantly attenuated [270,273]. With the same strains they demonstrate lower intracellular bacterial burdens after killing extracellular bacteria for 1 h with gentamicin (100µg/mL) [270,273].…”

“…Using these strains, in a fluorescence flow cytometry platform, they show the LPS core facilitates adherence to both dendritic and Langerhans cells, as mutants where the oligosaccharide core are truncated or covered by the O-polysaccharide are significantly attenuated [270,273]. With the same strains they demonstrate lower intracellular bacterial burdens after killing extracellular bacteria for 1 h with gentamicin (100µg/mL) [270,273]. However, the data failed to provide a clear preventative role, as Y. pestis LPS is temperature modulated (hexa-acylated (26°C) to tetra-acylated (37°C); discussed in chapter 1).…”

“…DC-SIGN (CD209) and Langrin (CD207) were demonstrated to bind LPS oligosaccharide core of Y. pestis [270,272]. Y. pestis does not have an O-antigen, but an oligosaccharide outer core attached to lipid A (for review see [67]).…”