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Soluble C-Type Lectin-Receptor Ligands Stimulate ROS Production in Dendritic Cells and Potentiate Killing of MRSA as Well as the MRSA Induced IL-12 Production

Methicillin resistant Staphylococcus aureus (MRSA) has developed resistance to most β-lactam antibiotics leaving few treatment options against infections with MRSA. Through mannose receptors, mannan potentiates IL-12 production induced by Gram-positive bacteria, a cytokine crucial in the clearance o...

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Autores principales: Eld, Helene M. S., Johnsen, Peter R., Nielsen, Emilie M., Jørgensen, Frederikke Z., Lindstrøm-Svendsen, Marie, Baldry, Mara, Ingmer, Hanne, Frøkiær, Hanne
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8977849/
https://www.ncbi.nlm.nih.gov/pubmed/35386713
http://dx.doi.org/10.3389/fimmu.2022.845881
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author Eld, Helene M. S.
Johnsen, Peter R.
Nielsen, Emilie M.
Jørgensen, Frederikke Z.
Lindstrøm-Svendsen, Marie
Baldry, Mara
Ingmer, Hanne
Frøkiær, Hanne
author_facet Eld, Helene M. S.
Johnsen, Peter R.
Nielsen, Emilie M.
Jørgensen, Frederikke Z.
Lindstrøm-Svendsen, Marie
Baldry, Mara
Ingmer, Hanne
Frøkiær, Hanne
author_sort Eld, Helene M. S.
collection PubMed
description Methicillin resistant Staphylococcus aureus (MRSA) has developed resistance to most β-lactam antibiotics leaving few treatment options against infections with MRSA. Through mannose receptors, mannan potentiates IL-12 production induced by Gram-positive bacteria, a cytokine crucial in the clearance of S. aureus infection. We investigated the IL-12 potentiating effect of mannan pre-treatment of bone marrow-derived dendritic cells prior to stimulation with clinical MRSA strains. Mannan almost doubled IL-12 as well as IFN-β production in response to USA300, also when USA300 was treated with the β-lactam cefoxitin. The MRSA-induced IL-12 production was dependent on bacterial uptake and reactive oxygen species (ROS). Mannan alone induced ROS production, and in combination with USA300, the ROS produced corresponded to the sum induced by mannan and USA300. Addition of a monoclonal antibody against the mannose receptor likewise enhanced USA300-induced IL-12 and induced ROS production. Mannan addition further increased the endocytosis as well as the rate of endosomal killing of bacteria. Pre-treatment with soluble β-glucans also induced ROS and potentiated the USA300-induced IL-12 indicating that other C-type receptors may play a similar role. In the presence of the pro-inflammatory mediators, GM-CSF or IFN-γ, the mannan-enhanced IL-12 production increased further. The USA300-induced and the mannan-facilitated enhanced IFN-β and IL-12 showed same dependency on MAPK c-Jun N-terminal kinase signaling, suggesting that mannan enhances the signals already induced by the bacteria, rather than changing them. We suggest that the C-type lectin-induced ROS production is a key factor in the IFN-β and IL-12 potentiation.
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spelling pubmed-89778492022-04-05 Soluble C-Type Lectin-Receptor Ligands Stimulate ROS Production in Dendritic Cells and Potentiate Killing of MRSA as Well as the MRSA Induced IL-12 Production Eld, Helene M. S. Johnsen, Peter R. Nielsen, Emilie M. Jørgensen, Frederikke Z. Lindstrøm-Svendsen, Marie Baldry, Mara Ingmer, Hanne Frøkiær, Hanne Front Immunol Immunology Methicillin resistant Staphylococcus aureus (MRSA) has developed resistance to most β-lactam antibiotics leaving few treatment options against infections with MRSA. Through mannose receptors, mannan potentiates IL-12 production induced by Gram-positive bacteria, a cytokine crucial in the clearance of S. aureus infection. We investigated the IL-12 potentiating effect of mannan pre-treatment of bone marrow-derived dendritic cells prior to stimulation with clinical MRSA strains. Mannan almost doubled IL-12 as well as IFN-β production in response to USA300, also when USA300 was treated with the β-lactam cefoxitin. The MRSA-induced IL-12 production was dependent on bacterial uptake and reactive oxygen species (ROS). Mannan alone induced ROS production, and in combination with USA300, the ROS produced corresponded to the sum induced by mannan and USA300. Addition of a monoclonal antibody against the mannose receptor likewise enhanced USA300-induced IL-12 and induced ROS production. Mannan addition further increased the endocytosis as well as the rate of endosomal killing of bacteria. Pre-treatment with soluble β-glucans also induced ROS and potentiated the USA300-induced IL-12 indicating that other C-type receptors may play a similar role. In the presence of the pro-inflammatory mediators, GM-CSF or IFN-γ, the mannan-enhanced IL-12 production increased further. The USA300-induced and the mannan-facilitated enhanced IFN-β and IL-12 showed same dependency on MAPK c-Jun N-terminal kinase signaling, suggesting that mannan enhances the signals already induced by the bacteria, rather than changing them. We suggest that the C-type lectin-induced ROS production is a key factor in the IFN-β and IL-12 potentiation. Frontiers Media S.A. 2022-03-21 /pmc/articles/PMC8977849/ /pubmed/35386713 http://dx.doi.org/10.3389/fimmu.2022.845881 Text en Copyright © 2022 Eld, Johnsen, Nielsen, Jørgensen, Lindstrøm-Svendsen, Baldry, Ingmer and Frøkiær https://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
Eld, Helene M. S.
Johnsen, Peter R.
Nielsen, Emilie M.
Jørgensen, Frederikke Z.
Lindstrøm-Svendsen, Marie
Baldry, Mara
Ingmer, Hanne
Frøkiær, Hanne
Soluble C-Type Lectin-Receptor Ligands Stimulate ROS Production in Dendritic Cells and Potentiate Killing of MRSA as Well as the MRSA Induced IL-12 Production
title Soluble C-Type Lectin-Receptor Ligands Stimulate ROS Production in Dendritic Cells and Potentiate Killing of MRSA as Well as the MRSA Induced IL-12 Production
title_full Soluble C-Type Lectin-Receptor Ligands Stimulate ROS Production in Dendritic Cells and Potentiate Killing of MRSA as Well as the MRSA Induced IL-12 Production
title_fullStr Soluble C-Type Lectin-Receptor Ligands Stimulate ROS Production in Dendritic Cells and Potentiate Killing of MRSA as Well as the MRSA Induced IL-12 Production
title_full_unstemmed Soluble C-Type Lectin-Receptor Ligands Stimulate ROS Production in Dendritic Cells and Potentiate Killing of MRSA as Well as the MRSA Induced IL-12 Production
title_short Soluble C-Type Lectin-Receptor Ligands Stimulate ROS Production in Dendritic Cells and Potentiate Killing of MRSA as Well as the MRSA Induced IL-12 Production
title_sort soluble c-type lectin-receptor ligands stimulate ros production in dendritic cells and potentiate killing of mrsa as well as the mrsa induced il-12 production
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8977849/
https://www.ncbi.nlm.nih.gov/pubmed/35386713
http://dx.doi.org/10.3389/fimmu.2022.845881
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