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Bactericidal/Permeability-Increasing Protein Is an Enhancer of Bacterial Lipoprotein Recognition

Adequate perception of immunologically important pathogen-associated molecular patterns like lipopolysaccharide and bacterial lipoproteins is essential for efficient innate and adaptive immune responses. In the context of Gram-negative infection, bactericidal/permeability-increasing protein (BPI) ne...

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Autores principales: Bülow, Sigrid, Zeller, Lisa, Werner, Maren, Toelge, Martina, Holzinger, Jonas, Entzian, Clemens, Schubert, Thomas, Waldow, Franziska, Gisch, Nicolas, Hammerschmidt, Sven, Gessner, André
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6293271/
https://www.ncbi.nlm.nih.gov/pubmed/30581431
http://dx.doi.org/10.3389/fimmu.2018.02768
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author Bülow, Sigrid
Zeller, Lisa
Werner, Maren
Toelge, Martina
Holzinger, Jonas
Entzian, Clemens
Schubert, Thomas
Waldow, Franziska
Gisch, Nicolas
Hammerschmidt, Sven
Gessner, André
author_facet Bülow, Sigrid
Zeller, Lisa
Werner, Maren
Toelge, Martina
Holzinger, Jonas
Entzian, Clemens
Schubert, Thomas
Waldow, Franziska
Gisch, Nicolas
Hammerschmidt, Sven
Gessner, André
author_sort Bülow, Sigrid
collection PubMed
description Adequate perception of immunologically important pathogen-associated molecular patterns like lipopolysaccharide and bacterial lipoproteins is essential for efficient innate and adaptive immune responses. In the context of Gram-negative infection, bactericidal/permeability-increasing protein (BPI) neutralizes endotoxic activity of lipopolysaccharides, and thus prohibits hyperactivation. So far, no immunological function of BPI has been described in Gram-positive infections. Here, we show a significant elevation of BPI in Gram-positive meningitis and, surprisingly, a positive correlation between BPI and pro-inflammatory markers like TNFα. To clarify the underlying mechanisms, we identify BPI ligands of Gram-positive origin, specifically bacterial lipopeptides and lipoteichoic acids, and determine essential structural motifs for this interaction. Importantly, the interaction of BPI with these newly defined ligands significantly enhances the immune response in peripheral blood mononuclear cells (PBMCs) mediated by Gram-positive bacteria, and thereby ensures their sensitive perception. In conclusion, we define BPI as an immune enhancing pattern recognition molecule in Gram-positive infections.
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spelling pubmed-62932712018-12-21 Bactericidal/Permeability-Increasing Protein Is an Enhancer of Bacterial Lipoprotein Recognition Bülow, Sigrid Zeller, Lisa Werner, Maren Toelge, Martina Holzinger, Jonas Entzian, Clemens Schubert, Thomas Waldow, Franziska Gisch, Nicolas Hammerschmidt, Sven Gessner, André Front Immunol Immunology Adequate perception of immunologically important pathogen-associated molecular patterns like lipopolysaccharide and bacterial lipoproteins is essential for efficient innate and adaptive immune responses. In the context of Gram-negative infection, bactericidal/permeability-increasing protein (BPI) neutralizes endotoxic activity of lipopolysaccharides, and thus prohibits hyperactivation. So far, no immunological function of BPI has been described in Gram-positive infections. Here, we show a significant elevation of BPI in Gram-positive meningitis and, surprisingly, a positive correlation between BPI and pro-inflammatory markers like TNFα. To clarify the underlying mechanisms, we identify BPI ligands of Gram-positive origin, specifically bacterial lipopeptides and lipoteichoic acids, and determine essential structural motifs for this interaction. Importantly, the interaction of BPI with these newly defined ligands significantly enhances the immune response in peripheral blood mononuclear cells (PBMCs) mediated by Gram-positive bacteria, and thereby ensures their sensitive perception. In conclusion, we define BPI as an immune enhancing pattern recognition molecule in Gram-positive infections. Frontiers Media S.A. 2018-12-05 /pmc/articles/PMC6293271/ /pubmed/30581431 http://dx.doi.org/10.3389/fimmu.2018.02768 Text en Copyright © 2018 Bülow, Zeller, Werner, Toelge, Holzinger, Entzian, Schubert, Waldow, Gisch, Hammerschmidt and Gessner. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Bülow, Sigrid
Zeller, Lisa
Werner, Maren
Toelge, Martina
Holzinger, Jonas
Entzian, Clemens
Schubert, Thomas
Waldow, Franziska
Gisch, Nicolas
Hammerschmidt, Sven
Gessner, André
Bactericidal/Permeability-Increasing Protein Is an Enhancer of Bacterial Lipoprotein Recognition
title Bactericidal/Permeability-Increasing Protein Is an Enhancer of Bacterial Lipoprotein Recognition
title_full Bactericidal/Permeability-Increasing Protein Is an Enhancer of Bacterial Lipoprotein Recognition
title_fullStr Bactericidal/Permeability-Increasing Protein Is an Enhancer of Bacterial Lipoprotein Recognition
title_full_unstemmed Bactericidal/Permeability-Increasing Protein Is an Enhancer of Bacterial Lipoprotein Recognition
title_short Bactericidal/Permeability-Increasing Protein Is an Enhancer of Bacterial Lipoprotein Recognition
title_sort bactericidal/permeability-increasing protein is an enhancer of bacterial lipoprotein recognition
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6293271/
https://www.ncbi.nlm.nih.gov/pubmed/30581431
http://dx.doi.org/10.3389/fimmu.2018.02768
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