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Complex Involvement of Interleukin-26 in Bacterial Lung Infection
Pneumonia is a global cause of mortality, and this provides a strong incentive to improve the mechanistic understanding of innate immune responses in the lungs. Here, we characterized the involvement of the cytokine interleukin (IL)-26 in bacterial lung infection. We observed markedly increased conc...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8581676/ https://www.ncbi.nlm.nih.gov/pubmed/34777376 http://dx.doi.org/10.3389/fimmu.2021.761317 |
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author | Che, Karlhans F. Paulsson, Magnus Piersiala, Krzysztof Sax, Jakob Mboob, Ibrahim Rahman, Mizanur Rekha, Rokeya S. Säfholm, Jesper Adner, Mikael Bergman, Peter Cardell, Lars-Olaf Riesbeck, Kristian Lindén, Anders |
author_facet | Che, Karlhans F. Paulsson, Magnus Piersiala, Krzysztof Sax, Jakob Mboob, Ibrahim Rahman, Mizanur Rekha, Rokeya S. Säfholm, Jesper Adner, Mikael Bergman, Peter Cardell, Lars-Olaf Riesbeck, Kristian Lindén, Anders |
author_sort | Che, Karlhans F. |
collection | PubMed |
description | Pneumonia is a global cause of mortality, and this provides a strong incentive to improve the mechanistic understanding of innate immune responses in the lungs. Here, we characterized the involvement of the cytokine interleukin (IL)-26 in bacterial lung infection. We observed markedly increased concentrations of IL-26 in lower airway samples from patients with bacterial pneumonia and these correlated with blood neutrophil concentrations. Moreover, pathogen-associated molecular patterns (PAMPs) from both Gram-negative and -positive bacteria increased extracellular IL-26 concentrations in conditioned media from human models of alveolar epithelial cells, macrophages, and neutrophils in vitro. Stimulation with IL-26 inhibited the inherent release of neutrophil elastase and myeloperoxidase in unexposed neutrophils. This stimulation also inhibited the expression of activity makers in neutrophils exposed to Klebsiella pneumoniae. In addition, priming of human lung tissue ex vivo with exogenous IL-26 potentiated the endotoxin-induced increase in mRNA for other cytokines involved in the innate immune response, including the master Th17-regulator IL-23 and the archetype inhibitory cytokine IL-10. Finally, neutralization of endogenous IL-26 clearly increased the growth of Klebsiella pneumoniae in the macrophage culture. These findings suggest that IL-26 is involved in bacterial lung infection in a complex manner, by modulating critical aspects of innate immune responses locally and systemically in a seemingly purposeful manner and by contributing to the killing of bacteria in a way that resembles an antimicrobial peptide. Thus, IL-26 displays both diagnostic and therapeutic potential in pneumonia and deserves to be further evaluated in these respects. |
format | Online Article Text |
id | pubmed-8581676 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-85816762021-11-12 Complex Involvement of Interleukin-26 in Bacterial Lung Infection Che, Karlhans F. Paulsson, Magnus Piersiala, Krzysztof Sax, Jakob Mboob, Ibrahim Rahman, Mizanur Rekha, Rokeya S. Säfholm, Jesper Adner, Mikael Bergman, Peter Cardell, Lars-Olaf Riesbeck, Kristian Lindén, Anders Front Immunol Immunology Pneumonia is a global cause of mortality, and this provides a strong incentive to improve the mechanistic understanding of innate immune responses in the lungs. Here, we characterized the involvement of the cytokine interleukin (IL)-26 in bacterial lung infection. We observed markedly increased concentrations of IL-26 in lower airway samples from patients with bacterial pneumonia and these correlated with blood neutrophil concentrations. Moreover, pathogen-associated molecular patterns (PAMPs) from both Gram-negative and -positive bacteria increased extracellular IL-26 concentrations in conditioned media from human models of alveolar epithelial cells, macrophages, and neutrophils in vitro. Stimulation with IL-26 inhibited the inherent release of neutrophil elastase and myeloperoxidase in unexposed neutrophils. This stimulation also inhibited the expression of activity makers in neutrophils exposed to Klebsiella pneumoniae. In addition, priming of human lung tissue ex vivo with exogenous IL-26 potentiated the endotoxin-induced increase in mRNA for other cytokines involved in the innate immune response, including the master Th17-regulator IL-23 and the archetype inhibitory cytokine IL-10. Finally, neutralization of endogenous IL-26 clearly increased the growth of Klebsiella pneumoniae in the macrophage culture. These findings suggest that IL-26 is involved in bacterial lung infection in a complex manner, by modulating critical aspects of innate immune responses locally and systemically in a seemingly purposeful manner and by contributing to the killing of bacteria in a way that resembles an antimicrobial peptide. Thus, IL-26 displays both diagnostic and therapeutic potential in pneumonia and deserves to be further evaluated in these respects. Frontiers Media S.A. 2021-10-28 /pmc/articles/PMC8581676/ /pubmed/34777376 http://dx.doi.org/10.3389/fimmu.2021.761317 Text en Copyright © 2021 Che, Paulsson, Piersiala, Sax, Mboob, Rahman, Rekha, Säfholm, Adner, Bergman, Cardell, Riesbeck and Lindén 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 Che, Karlhans F. Paulsson, Magnus Piersiala, Krzysztof Sax, Jakob Mboob, Ibrahim Rahman, Mizanur Rekha, Rokeya S. Säfholm, Jesper Adner, Mikael Bergman, Peter Cardell, Lars-Olaf Riesbeck, Kristian Lindén, Anders Complex Involvement of Interleukin-26 in Bacterial Lung Infection |
title | Complex Involvement of Interleukin-26 in Bacterial Lung Infection |
title_full | Complex Involvement of Interleukin-26 in Bacterial Lung Infection |
title_fullStr | Complex Involvement of Interleukin-26 in Bacterial Lung Infection |
title_full_unstemmed | Complex Involvement of Interleukin-26 in Bacterial Lung Infection |
title_short | Complex Involvement of Interleukin-26 in Bacterial Lung Infection |
title_sort | complex involvement of interleukin-26 in bacterial lung infection |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8581676/ https://www.ncbi.nlm.nih.gov/pubmed/34777376 http://dx.doi.org/10.3389/fimmu.2021.761317 |
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