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Antimicrobial Peptide Omiganan Enhances Interferon Responses to Endosomal Toll‐Like Receptor Ligands in Human Peripheral Blood Mononuclear Cells

LL‐37 is a cationic antimicrobial peptide and the sole human member of cathelicidins. Besides its bactericidal properties, LL‐37 is known to have direct immunomodulatory effects, among which enhancement of antiviral responses via endosomal toll‐like receptors (TLRs). Omiganan pentahydrochloride is a...

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Autores principales: Grievink, Hendrika W., Jirka, Silvana M. G., Woutman, Tess D., Schoonakker, Mascha, Rissmann, Robert, Malone, Karen E., Feiss, Gary, Moerland, Matthijs
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7485948/
https://www.ncbi.nlm.nih.gov/pubmed/32314872
http://dx.doi.org/10.1111/cts.12789
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author Grievink, Hendrika W.
Jirka, Silvana M. G.
Woutman, Tess D.
Schoonakker, Mascha
Rissmann, Robert
Malone, Karen E.
Feiss, Gary
Moerland, Matthijs
author_facet Grievink, Hendrika W.
Jirka, Silvana M. G.
Woutman, Tess D.
Schoonakker, Mascha
Rissmann, Robert
Malone, Karen E.
Feiss, Gary
Moerland, Matthijs
author_sort Grievink, Hendrika W.
collection PubMed
description LL‐37 is a cationic antimicrobial peptide and the sole human member of cathelicidins. Besides its bactericidal properties, LL‐37 is known to have direct immunomodulatory effects, among which enhancement of antiviral responses via endosomal toll‐like receptors (TLRs). Omiganan pentahydrochloride is a synthetic cationic peptide in clinical development. Previously, omiganan was primarily known for its direct bactericidal and antifungal properties. We investigated whether omiganan enhances endosomal TLR responses, similar to LL‐37. Human peripheral blood mononuclear cells were treated with endosomal TLR3, −7, −8, and −9 ligands in the presence of omiganan. Omiganan enhanced TLR‐mediated interferon‐α release. Subsequent experiments with TLR9 ligands showed that plasmacytoid dendritic cells were main contributors to omiganan‐enhanced IFN production. Based on this type I interferon‐enhancing effect, omiganan may qualify as potential treatment modality for virus‐driven diseases. The molecular mechanism by which omiganan enhances endosomal TLR responses remains to be elucidated.
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spelling pubmed-74859482020-09-18 Antimicrobial Peptide Omiganan Enhances Interferon Responses to Endosomal Toll‐Like Receptor Ligands in Human Peripheral Blood Mononuclear Cells Grievink, Hendrika W. Jirka, Silvana M. G. Woutman, Tess D. Schoonakker, Mascha Rissmann, Robert Malone, Karen E. Feiss, Gary Moerland, Matthijs Clin Transl Sci Research LL‐37 is a cationic antimicrobial peptide and the sole human member of cathelicidins. Besides its bactericidal properties, LL‐37 is known to have direct immunomodulatory effects, among which enhancement of antiviral responses via endosomal toll‐like receptors (TLRs). Omiganan pentahydrochloride is a synthetic cationic peptide in clinical development. Previously, omiganan was primarily known for its direct bactericidal and antifungal properties. We investigated whether omiganan enhances endosomal TLR responses, similar to LL‐37. Human peripheral blood mononuclear cells were treated with endosomal TLR3, −7, −8, and −9 ligands in the presence of omiganan. Omiganan enhanced TLR‐mediated interferon‐α release. Subsequent experiments with TLR9 ligands showed that plasmacytoid dendritic cells were main contributors to omiganan‐enhanced IFN production. Based on this type I interferon‐enhancing effect, omiganan may qualify as potential treatment modality for virus‐driven diseases. The molecular mechanism by which omiganan enhances endosomal TLR responses remains to be elucidated. John Wiley and Sons Inc. 2020-04-21 2020-09 /pmc/articles/PMC7485948/ /pubmed/32314872 http://dx.doi.org/10.1111/cts.12789 Text en © 2020 The Authors. Clinical and Translational Science published by Wiley Periodicals, Inc. on behalf of the American Society of Clinical Pharmacology and Therapeutics. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Research
Grievink, Hendrika W.
Jirka, Silvana M. G.
Woutman, Tess D.
Schoonakker, Mascha
Rissmann, Robert
Malone, Karen E.
Feiss, Gary
Moerland, Matthijs
Antimicrobial Peptide Omiganan Enhances Interferon Responses to Endosomal Toll‐Like Receptor Ligands in Human Peripheral Blood Mononuclear Cells
title Antimicrobial Peptide Omiganan Enhances Interferon Responses to Endosomal Toll‐Like Receptor Ligands in Human Peripheral Blood Mononuclear Cells
title_full Antimicrobial Peptide Omiganan Enhances Interferon Responses to Endosomal Toll‐Like Receptor Ligands in Human Peripheral Blood Mononuclear Cells
title_fullStr Antimicrobial Peptide Omiganan Enhances Interferon Responses to Endosomal Toll‐Like Receptor Ligands in Human Peripheral Blood Mononuclear Cells
title_full_unstemmed Antimicrobial Peptide Omiganan Enhances Interferon Responses to Endosomal Toll‐Like Receptor Ligands in Human Peripheral Blood Mononuclear Cells
title_short Antimicrobial Peptide Omiganan Enhances Interferon Responses to Endosomal Toll‐Like Receptor Ligands in Human Peripheral Blood Mononuclear Cells
title_sort antimicrobial peptide omiganan enhances interferon responses to endosomal toll‐like receptor ligands in human peripheral blood mononuclear cells
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7485948/
https://www.ncbi.nlm.nih.gov/pubmed/32314872
http://dx.doi.org/10.1111/cts.12789
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