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/Subject (Langerhans cells are key sentinel cells of the skin and mucosal lining. They sense microorganisms through their repertoire of pattern-recognition receptors to mount and direct appropriate immune responses. We recently demonstrated that human Langerhans cells interact with the Gram-positive pathogen Staphylococcus aureus through the Langerhans cell-specific receptor langerin \(CD207\). It was previously hypothesized that two linked single nucleotide polymorphisms \(SNPs; N288D and K313I\) in the carbohydrate recognition domain of langerin would affect interaction with microorganisms. We show that recognition of S. aureus by recombinant langerin molecules is abrogated in the co-inheriting SNP variant, which is mainly explained by the N288D SNP and further enhanced by K313I. Moreover, introduction of SNP N288D in ectopically-expressed langerin affected cellular distribution of the receptor such that langerin displayed enhanced plasma membraneexpression. Despite this increased binding of S. aureus by the langerin double SNP variant, uptake of bacteria by this langerin variant was compromised. Our findings indicate that in a proportion of the human population, the recognition and uptake of S. aureus by Langerhans cells may be affected, which could have important consequences for proper immune activation and S. aureus-associated disease.)
/Title (A Common Genetic Variation in Langerin \(CD207\) Compromises Cellular Uptake of Staphylococcus aureus)
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van Dalen R.; Fuchsberger F.F.; Rademacher C.; van Strijp J.A.G.; van Sorge N.M.
A Common Genetic Variation in Langerin (CD207) Compromises Cellular Uptake of <b><i>Staphylococcus aureus</i></b>
This article is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND). Usage and distribution for commercial purposes as well as any distribution of modified material requires written permission. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
Langerhans cells are key sentinel cells of the skin and mucosal lining. They sense microorganisms through their repertoire of pattern-recognition receptors to mount and direct appropriate immune responses. We recently demonstrated that human Langerhans cells interact with the Gram-positive pathogen Staphylococcus aureus through the Langerhans cell-specific receptor langerin (CD207). It was previously hypothesized that two linked single nucleotide polymorphisms (SNPs; N288D and K313I) in the carbohydrate recognition domain of langerin would affect interaction with microorganisms. We show that recognition of S. aureus by recombinant langerin molecules is abrogated in the co-inheriting SNP variant, which is mainly explained by the N288D SNP and further enhanced by K313I. Moreover, introduction of SNP N288D in ectopically-expressed langerin affected cellular distribution of the receptor such that langerin displayed enhanced plasma membraneexpression. Despite this increased binding of S. aureus by the langerin double SNP variant, uptake of bacteria by this langerin variant was compromised. Our findings indicate that in a proportion of the human population, the recognition and uptake of S. aureus by Langerhans cells may be affected, which could have important consequences for proper immune activation and S. aureus-associated disease.
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