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C-type lectin Langerin is a beta-glucan receptor on human Langerhans cells that recognizes opportunistic and pathogenic fungi.

de Jong MA, Vriend LE, Theelen B, Taylor ME, Fluitsma D, Boekhout T, Geijtenbeek TB - Mol. Immunol. (2010)

Bottom Line: We have screened a large panel of fungi for recognition by human Langerin and, strikingly, we observed strong binding of Langerin to a variety of Candida and Saccharomyces species and Malassezia furfur, but very weak binding was observed to Cryptococcus gattii and Cryptococcus neoformans.Notably, Langerin is the primary fungal receptor on LCs, since the interaction of LCs with the different fungi was blocked by antibodies against Langerin.Langerin recognizes both mannose and beta-glucans present on fungal cell walls and our data demonstrate that Langerin is the major fungal pathogen receptor on human LCs that recognizes pathogenic and commensal fungi.

View Article: PubMed Central - PubMed

Affiliation: Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.

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Langerin is the primary receptor for fungi on LCs. (A) CD1a, Langerin, dectin-1 and DC-SIGN expression on primary immature LCs. Thin line represents isotype control, filled histogram represents specific staining. (B) Binding of different fungi to human LCs was investigated. FITC-labelled fungi were incubated with LCs at MOI 10. Specificity was determined by mannan, blocking antibodies against Langerin and dectin-1, or isotype controls. Binding was measured by flow cytometry. Data represent results from at least three different donors. Error bars represent standard deviation of triplicates.
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fig5: Langerin is the primary receptor for fungi on LCs. (A) CD1a, Langerin, dectin-1 and DC-SIGN expression on primary immature LCs. Thin line represents isotype control, filled histogram represents specific staining. (B) Binding of different fungi to human LCs was investigated. FITC-labelled fungi were incubated with LCs at MOI 10. Specificity was determined by mannan, blocking antibodies against Langerin and dectin-1, or isotype controls. Binding was measured by flow cytometry. Data represent results from at least three different donors. Error bars represent standard deviation of triplicates.

Mentions: Opportunistic fungal infections often enter through the skin or mucosal tissues, where LCs are the predominant antigen presenting cells. Therefore, we investigated whether primary human LCs interact with different fungi. CD1a+ LCs isolated from human epidermis express high levels of Langerin, low levels of dectin-1 and no DC-SIGN (Fig. 5A). Both DC-SIGN and dectin-1 have been shown to bind fungi through mannan and β-glucan structures, respectively (Cambi et al., 2008; Brown et al., 2003). Primary LCs were incubated with fluorescently labelled C. albicans, C. krusei, Cr. neoformans, Cr. gattii, and zymosan and binding was measured by flow cytometry. Strikingly, LCs strongly interacted with C. albicans, C. krusei, and zymosan, but not with Cr. neoformans or Cr. gattii (Fig. 5B). The binding to C. albicans, C. krusei, and zymosan was primarily mediated via Langerin, since both mannan and specific antibodies against Langerin inhibited the binding to LCs (Fig. 5B). The blocking antibody against dectin-1 only weakly interfered with fungi binding to LCs, strongly suggesting that the contribution of dectin-1 on LCs is minor. Cr. neoformans and Cr. gattii failed to interact with LCs even at very high concentrations (data not shown). We observed a background binding of approximately 10%, which could be due to other receptors, such as complement receptor 3 expressed in low levels by LCs (Depanfilis et al., 1990; Netea et al., 2008).


C-type lectin Langerin is a beta-glucan receptor on human Langerhans cells that recognizes opportunistic and pathogenic fungi.

de Jong MA, Vriend LE, Theelen B, Taylor ME, Fluitsma D, Boekhout T, Geijtenbeek TB - Mol. Immunol. (2010)

Langerin is the primary receptor for fungi on LCs. (A) CD1a, Langerin, dectin-1 and DC-SIGN expression on primary immature LCs. Thin line represents isotype control, filled histogram represents specific staining. (B) Binding of different fungi to human LCs was investigated. FITC-labelled fungi were incubated with LCs at MOI 10. Specificity was determined by mannan, blocking antibodies against Langerin and dectin-1, or isotype controls. Binding was measured by flow cytometry. Data represent results from at least three different donors. Error bars represent standard deviation of triplicates.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2837148&req=5

fig5: Langerin is the primary receptor for fungi on LCs. (A) CD1a, Langerin, dectin-1 and DC-SIGN expression on primary immature LCs. Thin line represents isotype control, filled histogram represents specific staining. (B) Binding of different fungi to human LCs was investigated. FITC-labelled fungi were incubated with LCs at MOI 10. Specificity was determined by mannan, blocking antibodies against Langerin and dectin-1, or isotype controls. Binding was measured by flow cytometry. Data represent results from at least three different donors. Error bars represent standard deviation of triplicates.
Mentions: Opportunistic fungal infections often enter through the skin or mucosal tissues, where LCs are the predominant antigen presenting cells. Therefore, we investigated whether primary human LCs interact with different fungi. CD1a+ LCs isolated from human epidermis express high levels of Langerin, low levels of dectin-1 and no DC-SIGN (Fig. 5A). Both DC-SIGN and dectin-1 have been shown to bind fungi through mannan and β-glucan structures, respectively (Cambi et al., 2008; Brown et al., 2003). Primary LCs were incubated with fluorescently labelled C. albicans, C. krusei, Cr. neoformans, Cr. gattii, and zymosan and binding was measured by flow cytometry. Strikingly, LCs strongly interacted with C. albicans, C. krusei, and zymosan, but not with Cr. neoformans or Cr. gattii (Fig. 5B). The binding to C. albicans, C. krusei, and zymosan was primarily mediated via Langerin, since both mannan and specific antibodies against Langerin inhibited the binding to LCs (Fig. 5B). The blocking antibody against dectin-1 only weakly interfered with fungi binding to LCs, strongly suggesting that the contribution of dectin-1 on LCs is minor. Cr. neoformans and Cr. gattii failed to interact with LCs even at very high concentrations (data not shown). We observed a background binding of approximately 10%, which could be due to other receptors, such as complement receptor 3 expressed in low levels by LCs (Depanfilis et al., 1990; Netea et al., 2008).

Bottom Line: We have screened a large panel of fungi for recognition by human Langerin and, strikingly, we observed strong binding of Langerin to a variety of Candida and Saccharomyces species and Malassezia furfur, but very weak binding was observed to Cryptococcus gattii and Cryptococcus neoformans.Notably, Langerin is the primary fungal receptor on LCs, since the interaction of LCs with the different fungi was blocked by antibodies against Langerin.Langerin recognizes both mannose and beta-glucans present on fungal cell walls and our data demonstrate that Langerin is the major fungal pathogen receptor on human LCs that recognizes pathogenic and commensal fungi.

View Article: PubMed Central - PubMed

Affiliation: Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.

Show MeSH
Related in: MedlinePlus