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

Yang K, Park CG, Cheong C, Bulgheresi S, Zhang S, Zhang P, He Y, Jiang L, Huang H, Ding H, Wu Y, Wang S, Zhang L, Li A, Xia L, Bartra SS, Plano GV, Skurnik M, Klena JD, Chen T - Immunol. Cell Biol. (2015)

Bottom Line: However, when the bacterial core oligosaccharides are shielded or truncated, Y. pestis propensity to invade Langerhans and Langerin-expressing cells decreases.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 LCs by Y. pestis.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Immunology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.

ABSTRACT
Yersinia pestis is a Gram-negative bacterium that causes plague. After Y. pestis overcomes the skin barrier, it encounters antigen-presenting cells (APCs), 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 (LCs) 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 LCs 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 (DC-specific intercellular adhesion molecule 3 grabbing nonintegrin)-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 LCs by Y. pestis. Therefore, Langerin-mediated binding of Y. pestis to APCs may promote its dissemination and infection.

No MeSH data available.


Related in: MedlinePlus

Expression of Y. pestis O-antigen reduces pathogen dissemination and host death. (a) KIM6+ and KIM6+-O+ (O-antigen expressing) were inoculated in mice following the procedures described in the Methods section. After 24 h, the mice were killed, and the subiliac lymph nodes were separated, homogenised and spread on GC-base plates. The dissemination rate represents the CFU recovered from whole subiliac lymph nodes. The data presented were pooled from three independent experiments. The data represent the means±s.e.m. N=9. Statistical analysis was performed using Student's t-test. ***P<0.001. (b) Mouse survival in a dissemination model challenged with Y. pestis 1418 (KIM D27) or Y. pestis 1418-O+. The survival curve shows the animal survival time from the inoculation. The data presented were pooled from three independent experiments. Statistical analysis was performed using the log-rank test. *P<0.05.
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fig7: Expression of Y. pestis O-antigen reduces pathogen dissemination and host death. (a) KIM6+ and KIM6+-O+ (O-antigen expressing) were inoculated in mice following the procedures described in the Methods section. After 24 h, the mice were killed, and the subiliac lymph nodes were separated, homogenised and spread on GC-base plates. The dissemination rate represents the CFU recovered from whole subiliac lymph nodes. The data presented were pooled from three independent experiments. The data represent the means±s.e.m. N=9. Statistical analysis was performed using Student's t-test. ***P<0.001. (b) Mouse survival in a dissemination model challenged with Y. pestis 1418 (KIM D27) or Y. pestis 1418-O+. The survival curve shows the animal survival time from the inoculation. The data presented were pooled from three independent experiments. Statistical analysis was performed using the log-rank test. *P<0.05.

Mentions: We speculated that the interaction of Y. pestis with C-type lectin receptors promotes bacterial dissemination.9, 13 Given that the interaction appears to be mediated by core oligosaccharides and hLangerin, we hypothesised that shielding the exposed core oligosaccharides of Y. pestis would reduce its dissemination and consequently delay death in a murine model. To test this hypothesis, the Y. pestis strain KIM6, as well as the strain KIM D27 with and without O-antigen expression, were injected into mouse metacarpal paw pads. The KIM6 and KIM D27 strains were used in this experiment rather than KIM10 because KIM10 does not survive in mice.9, 13 For the dissemination assay, subiliac lymph nodes were collected, and the bacterial counts were determined, which allowed for the calculation of Y. pestis dissemination rates into the lymph nodes. In mice challenged with the strain KIM D27, the amount of time that the animals took to succumb to infection was recorded following inoculation. As indicated in Figure 7, the dissemination (Figure 7a) and death (Figure 7b) of O-antigen-expressing Y. pestis were significantly reduced. Notably, the expression of O-antigen did not affect Y. pesits infectivity when delivered intravenously, indicating that Y. pestis uptake by skin APCs mediate Y. pesits dissemination.19 In addition, the growth rate of Y. pestis was not dependent on O-antigen expression.


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

Yang K, Park CG, Cheong C, Bulgheresi S, Zhang S, Zhang P, He Y, Jiang L, Huang H, Ding H, Wu Y, Wang S, Zhang L, Li A, Xia L, Bartra SS, Plano GV, Skurnik M, Klena JD, Chen T - Immunol. Cell Biol. (2015)

Expression of Y. pestis O-antigen reduces pathogen dissemination and host death. (a) KIM6+ and KIM6+-O+ (O-antigen expressing) were inoculated in mice following the procedures described in the Methods section. After 24 h, the mice were killed, and the subiliac lymph nodes were separated, homogenised and spread on GC-base plates. The dissemination rate represents the CFU recovered from whole subiliac lymph nodes. The data presented were pooled from three independent experiments. The data represent the means±s.e.m. N=9. Statistical analysis was performed using Student's t-test. ***P<0.001. (b) Mouse survival in a dissemination model challenged with Y. pestis 1418 (KIM D27) or Y. pestis 1418-O+. The survival curve shows the animal survival time from the inoculation. The data presented were pooled from three independent experiments. Statistical analysis was performed using the log-rank test. *P<0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4612776&req=5

fig7: Expression of Y. pestis O-antigen reduces pathogen dissemination and host death. (a) KIM6+ and KIM6+-O+ (O-antigen expressing) were inoculated in mice following the procedures described in the Methods section. After 24 h, the mice were killed, and the subiliac lymph nodes were separated, homogenised and spread on GC-base plates. The dissemination rate represents the CFU recovered from whole subiliac lymph nodes. The data presented were pooled from three independent experiments. The data represent the means±s.e.m. N=9. Statistical analysis was performed using Student's t-test. ***P<0.001. (b) Mouse survival in a dissemination model challenged with Y. pestis 1418 (KIM D27) or Y. pestis 1418-O+. The survival curve shows the animal survival time from the inoculation. The data presented were pooled from three independent experiments. Statistical analysis was performed using the log-rank test. *P<0.05.
Mentions: We speculated that the interaction of Y. pestis with C-type lectin receptors promotes bacterial dissemination.9, 13 Given that the interaction appears to be mediated by core oligosaccharides and hLangerin, we hypothesised that shielding the exposed core oligosaccharides of Y. pestis would reduce its dissemination and consequently delay death in a murine model. To test this hypothesis, the Y. pestis strain KIM6, as well as the strain KIM D27 with and without O-antigen expression, were injected into mouse metacarpal paw pads. The KIM6 and KIM D27 strains were used in this experiment rather than KIM10 because KIM10 does not survive in mice.9, 13 For the dissemination assay, subiliac lymph nodes were collected, and the bacterial counts were determined, which allowed for the calculation of Y. pestis dissemination rates into the lymph nodes. In mice challenged with the strain KIM D27, the amount of time that the animals took to succumb to infection was recorded following inoculation. As indicated in Figure 7, the dissemination (Figure 7a) and death (Figure 7b) of O-antigen-expressing Y. pestis were significantly reduced. Notably, the expression of O-antigen did not affect Y. pesits infectivity when delivered intravenously, indicating that Y. pestis uptake by skin APCs mediate Y. pesits dissemination.19 In addition, the growth rate of Y. pestis was not dependent on O-antigen expression.

Bottom Line: However, when the bacterial core oligosaccharides are shielded or truncated, Y. pestis propensity to invade Langerhans and Langerin-expressing cells decreases.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 LCs by Y. pestis.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Immunology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.

ABSTRACT
Yersinia pestis is a Gram-negative bacterium that causes plague. After Y. pestis overcomes the skin barrier, it encounters antigen-presenting cells (APCs), 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 (LCs) 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 LCs 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 (DC-specific intercellular adhesion molecule 3 grabbing nonintegrin)-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 LCs by Y. pestis. Therefore, Langerin-mediated binding of Y. pestis to APCs may promote its dissemination and infection.

No MeSH data available.


Related in: MedlinePlus