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Role of Toll-Like Receptors 2 and 4 in Pulmonary Inflammation and Injury Induced by Pneumolysin in Mice

BACKGROUND: Pneumolysin (PLN) is an intracellular toxin of Streptococcus pneumoniae that has been implicated as a major virulence factor in infections caused by this pathogen. Conserved bacterial motifs are recognized by the immune system by pattern recognition receptors among which the family of To...

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Autores principales: Dessing, Mark C., Hirst, Robert A., de Vos, Alex F., van der Poll, Tom
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2776357/
https://www.ncbi.nlm.nih.gov/pubmed/19956717
http://dx.doi.org/10.1371/journal.pone.0007993
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author Dessing, Mark C.
Hirst, Robert A.
de Vos, Alex F.
van der Poll, Tom
author_facet Dessing, Mark C.
Hirst, Robert A.
de Vos, Alex F.
van der Poll, Tom
author_sort Dessing, Mark C.
collection PubMed
description BACKGROUND: Pneumolysin (PLN) is an intracellular toxin of Streptococcus pneumoniae that has been implicated as a major virulence factor in infections caused by this pathogen. Conserved bacterial motifs are recognized by the immune system by pattern recognition receptors among which the family of Toll-like receptors (TLRs) prominently features. The primary objective of the present study was to determine the role of TLR2 and TLR4 in lung inflammation induced by intrapulmonary delivery of PLN. METHODOLOGY/RESULTS: First, we confirmed that purified PLN activates cells via TLR4 (not via TLR2) in vitro, using human embryonic kidney cells transfected with either TLR2 or TLR4. Intranasal administration of PLN induced an inflammatory response in the pulmonary compartment of mice in vivo, as reflected by influx of neutrophils, release of proinflammatory cytokines and chemokines, and a rise in total protein concentrations in bronchoalveolar lavage fluid. These PLN-induced responses were dependent in part, not only on TLR4, but also on TLR2, as indicated by studies using TLR deficient mice. CONCLUSION: These data suggest that although purified PLN is recognized by TLR4 in vitro, PLN elicits lung inflammation in vivo by mechanisms that may involve multiple TLRs.
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spelling pubmed-27763572009-12-03 Role of Toll-Like Receptors 2 and 4 in Pulmonary Inflammation and Injury Induced by Pneumolysin in Mice Dessing, Mark C. Hirst, Robert A. de Vos, Alex F. van der Poll, Tom PLoS One Research Article BACKGROUND: Pneumolysin (PLN) is an intracellular toxin of Streptococcus pneumoniae that has been implicated as a major virulence factor in infections caused by this pathogen. Conserved bacterial motifs are recognized by the immune system by pattern recognition receptors among which the family of Toll-like receptors (TLRs) prominently features. The primary objective of the present study was to determine the role of TLR2 and TLR4 in lung inflammation induced by intrapulmonary delivery of PLN. METHODOLOGY/RESULTS: First, we confirmed that purified PLN activates cells via TLR4 (not via TLR2) in vitro, using human embryonic kidney cells transfected with either TLR2 or TLR4. Intranasal administration of PLN induced an inflammatory response in the pulmonary compartment of mice in vivo, as reflected by influx of neutrophils, release of proinflammatory cytokines and chemokines, and a rise in total protein concentrations in bronchoalveolar lavage fluid. These PLN-induced responses were dependent in part, not only on TLR4, but also on TLR2, as indicated by studies using TLR deficient mice. CONCLUSION: These data suggest that although purified PLN is recognized by TLR4 in vitro, PLN elicits lung inflammation in vivo by mechanisms that may involve multiple TLRs. Public Library of Science 2009-11-24 /pmc/articles/PMC2776357/ /pubmed/19956717 http://dx.doi.org/10.1371/journal.pone.0007993 Text en Dessing et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Dessing, Mark C.
Hirst, Robert A.
de Vos, Alex F.
van der Poll, Tom
Role of Toll-Like Receptors 2 and 4 in Pulmonary Inflammation and Injury Induced by Pneumolysin in Mice
title Role of Toll-Like Receptors 2 and 4 in Pulmonary Inflammation and Injury Induced by Pneumolysin in Mice
title_full Role of Toll-Like Receptors 2 and 4 in Pulmonary Inflammation and Injury Induced by Pneumolysin in Mice
title_fullStr Role of Toll-Like Receptors 2 and 4 in Pulmonary Inflammation and Injury Induced by Pneumolysin in Mice
title_full_unstemmed Role of Toll-Like Receptors 2 and 4 in Pulmonary Inflammation and Injury Induced by Pneumolysin in Mice
title_short Role of Toll-Like Receptors 2 and 4 in Pulmonary Inflammation and Injury Induced by Pneumolysin in Mice
title_sort role of toll-like receptors 2 and 4 in pulmonary inflammation and injury induced by pneumolysin in mice
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2776357/
https://www.ncbi.nlm.nih.gov/pubmed/19956717
http://dx.doi.org/10.1371/journal.pone.0007993
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