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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

Inhibition of hLangerin-mediated phagocytosis of Y. pestis by anti-hLangerin antibody, mannan and oligosaccharides. The expression levels of hcbLCs and hLCs are shown in panels (a) and (c), respectively. Y. pestis KIM10− cultured at 26 °C was incubated with hcbLCs (b) and hLCs (d) for 1.5 h and CHO-hLangerin cells for 2 h (e) in the presence or absence of purified FLAG-hLangerin, anti-CD66/-hLangerin/-hDC-SIGN antibodies, mannan, various oligosaccharides and a DC-SIGN-like protein (His-Mermaid). The experiments with hcbLCs and hLCs were performed using antibody treatment only. All reagents were added to the media 20 min before the addition of bacteria. The concentration of each reagent used in this experiment was based on previously published data.14, 15, 16 The phagocytosis rate of Y. pestis was determined by the recovery of bacteria following gentamicin treatment. Y. pseudotuberculosis serotype O:1a was used as a control strain that shows core-independent invasion of CHO cells. The data presented were pooled from three independent experiments. The data represent the means±s.e.m. N=9. Statistical analysis was performed using one-way analysis of variance and the Newman–Keuls test. ***P<0.001.
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fig5: Inhibition of hLangerin-mediated phagocytosis of Y. pestis by anti-hLangerin antibody, mannan and oligosaccharides. The expression levels of hcbLCs and hLCs are shown in panels (a) and (c), respectively. Y. pestis KIM10− cultured at 26 °C was incubated with hcbLCs (b) and hLCs (d) for 1.5 h and CHO-hLangerin cells for 2 h (e) in the presence or absence of purified FLAG-hLangerin, anti-CD66/-hLangerin/-hDC-SIGN antibodies, mannan, various oligosaccharides and a DC-SIGN-like protein (His-Mermaid). The experiments with hcbLCs and hLCs were performed using antibody treatment only. All reagents were added to the media 20 min before the addition of bacteria. The concentration of each reagent used in this experiment was based on previously published data.14, 15, 16 The phagocytosis rate of Y. pestis was determined by the recovery of bacteria following gentamicin treatment. Y. pseudotuberculosis serotype O:1a was used as a control strain that shows core-independent invasion of CHO cells. The data presented were pooled from three independent experiments. The data represent the means±s.e.m. N=9. Statistical analysis was performed using one-way analysis of variance and the Newman–Keuls test. ***P<0.001.

Mentions: hcbLCs express both hLangerin and hDC-SIGN (Figure 5a). We examined whether host–pathogen interactions could be inhibited by anti-hLangerin and anti-hDC-SIGN antibodies in these cells (Table 1). As shown in Figure 5b, when used individually, neither anti-hLangerin nor anti-hDC-SIGN antibodies affected the phagocytosis of Y. pestis KIM10− by hcbLCs. However, when these two antibodies were combined, the phagocytosis of KIM10− by hcbLCs was significantly reduced. Nevertheless, this reduction was not complete, suggesting that additional receptors for Y. pestis are present on the hcbLCs (Figure 5b).


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)

Inhibition of hLangerin-mediated phagocytosis of Y. pestis by anti-hLangerin antibody, mannan and oligosaccharides. The expression levels of hcbLCs and hLCs are shown in panels (a) and (c), respectively. Y. pestis KIM10− cultured at 26 °C was incubated with hcbLCs (b) and hLCs (d) for 1.5 h and CHO-hLangerin cells for 2 h (e) in the presence or absence of purified FLAG-hLangerin, anti-CD66/-hLangerin/-hDC-SIGN antibodies, mannan, various oligosaccharides and a DC-SIGN-like protein (His-Mermaid). The experiments with hcbLCs and hLCs were performed using antibody treatment only. All reagents were added to the media 20 min before the addition of bacteria. The concentration of each reagent used in this experiment was based on previously published data.14, 15, 16 The phagocytosis rate of Y. pestis was determined by the recovery of bacteria following gentamicin treatment. Y. pseudotuberculosis serotype O:1a was used as a control strain that shows core-independent invasion of CHO cells. The data presented were pooled from three independent experiments. The data represent the means±s.e.m. N=9. Statistical analysis was performed using one-way analysis of variance and the Newman–Keuls test. ***P<0.001.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig5: Inhibition of hLangerin-mediated phagocytosis of Y. pestis by anti-hLangerin antibody, mannan and oligosaccharides. The expression levels of hcbLCs and hLCs are shown in panels (a) and (c), respectively. Y. pestis KIM10− cultured at 26 °C was incubated with hcbLCs (b) and hLCs (d) for 1.5 h and CHO-hLangerin cells for 2 h (e) in the presence or absence of purified FLAG-hLangerin, anti-CD66/-hLangerin/-hDC-SIGN antibodies, mannan, various oligosaccharides and a DC-SIGN-like protein (His-Mermaid). The experiments with hcbLCs and hLCs were performed using antibody treatment only. All reagents were added to the media 20 min before the addition of bacteria. The concentration of each reagent used in this experiment was based on previously published data.14, 15, 16 The phagocytosis rate of Y. pestis was determined by the recovery of bacteria following gentamicin treatment. Y. pseudotuberculosis serotype O:1a was used as a control strain that shows core-independent invasion of CHO cells. The data presented were pooled from three independent experiments. The data represent the means±s.e.m. N=9. Statistical analysis was performed using one-way analysis of variance and the Newman–Keuls test. ***P<0.001.
Mentions: hcbLCs express both hLangerin and hDC-SIGN (Figure 5a). We examined whether host–pathogen interactions could be inhibited by anti-hLangerin and anti-hDC-SIGN antibodies in these cells (Table 1). As shown in Figure 5b, when used individually, neither anti-hLangerin nor anti-hDC-SIGN antibodies affected the phagocytosis of Y. pestis KIM10− by hcbLCs. However, when these two antibodies were combined, the phagocytosis of KIM10− by hcbLCs was significantly reduced. Nevertheless, this reduction was not complete, suggesting that additional receptors for Y. pestis are present on the hcbLCs (Figure 5b).

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