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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doaj-127ddd59154042b79c8b8faf379771382020-11-24T21:44:57ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-12-01910.3389/fimmu.2018.02768412625Bactericidal/Permeability-Increasing Protein Is an Enhancer of Bacterial Lipoprotein RecognitionSigrid Bülow0Lisa Zeller1Maren Werner2Martina Toelge3Jonas Holzinger4Clemens Entzian5Thomas Schubert6Franziska Waldow7Nicolas Gisch8Sven Hammerschmidt9André Gessner10Institute of Clinical Microbiology and Hygiene, University Hospital Regensburg, Regensburg, GermanyInstitute of Clinical Microbiology and Hygiene, University Hospital Regensburg, Regensburg, GermanyInstitute of Clinical Microbiology and Hygiene, University Hospital Regensburg, Regensburg, GermanyInstitute of Clinical Microbiology and Hygiene, University Hospital Regensburg, Regensburg, GermanyInstitute of Clinical Microbiology and Hygiene, University Hospital Regensburg, Regensburg, Germany2bind GmbH, Am Biopark, Regensburg, Germany2bind GmbH, Am Biopark, Regensburg, GermanyDivision of Bioanalytical Chemistry, Priority Area Infections, Research Center Borstel, Leibniz Lung Center, Borstel, GermanyDivision of Bioanalytical Chemistry, Priority Area Infections, Research Center Borstel, Leibniz Lung Center, Borstel, GermanyDepartment of Molecular Genetics and Infection Biology, Center for Functional Genomcis of Microbes, Interfaculty Institute for Genetics and Functional Genomics, University of Greifswald, Greifswald, GermanyInstitute of Clinical Microbiology and Hygiene, University Hospital Regensburg, Regensburg, GermanyAdequate 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.https://www.frontiersin.org/article/10.3389/fimmu.2018.02768/fullbactericidal/permeability-increasing proteinpro-inflammatorybacterial lipoproteinlipoteichoic acidStreptococcus pneumoniaeGram-positive |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Sigrid Bülow Lisa Zeller Maren Werner Martina Toelge Jonas Holzinger Clemens Entzian Thomas Schubert Franziska Waldow Nicolas Gisch Sven Hammerschmidt André Gessner |
spellingShingle |
Sigrid Bülow Lisa Zeller Maren Werner Martina Toelge Jonas Holzinger Clemens Entzian Thomas Schubert Franziska Waldow Nicolas Gisch Sven Hammerschmidt André Gessner Bactericidal/Permeability-Increasing Protein Is an Enhancer of Bacterial Lipoprotein Recognition Frontiers in Immunology bactericidal/permeability-increasing protein pro-inflammatory bacterial lipoprotein lipoteichoic acid Streptococcus pneumoniae Gram-positive |
author_facet |
Sigrid Bülow Lisa Zeller Maren Werner Martina Toelge Jonas Holzinger Clemens Entzian Thomas Schubert Franziska Waldow Nicolas Gisch Sven Hammerschmidt André Gessner |
author_sort |
Sigrid Bülow |
title |
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_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_sort |
bactericidal/permeability-increasing protein is an enhancer of bacterial lipoprotein recognition |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2018-12-01 |
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. |
topic |
bactericidal/permeability-increasing protein pro-inflammatory bacterial lipoprotein lipoteichoic acid Streptococcus pneumoniae Gram-positive |
url |
https://www.frontiersin.org/article/10.3389/fimmu.2018.02768/full |
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