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A decoy receptor 3 analogue reduces localised defects in phagocyte function in pneumococcal pneumonia

BACKGROUND: Therapeutic strategies to modulate the host response to bacterial pneumonia are needed to improve outcomes during community-acquired pneumonia. This study used mice with impaired Fas signalling to examine susceptibility to pneumococcal pneumonia and decoy receptor 3 analogue (DcR3-a) to...

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Autores principales: Marriott, Helen M, Daigneault, Marc, Thompson, Alfred A R, Walmsley, Sarah R, Gill, Sharonjit K, Witcher, Derrick R, Wroblewski, Victor J, Hellewell, Paul G, Whyte, Moira K B, Dockrell, David H
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Group 2012
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3505869/
https://www.ncbi.nlm.nih.gov/pubmed/22735687
http://dx.doi.org/10.1136/thoraxjnl-2012-201591
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author Marriott, Helen M
Daigneault, Marc
Thompson, Alfred A R
Walmsley, Sarah R
Gill, Sharonjit K
Witcher, Derrick R
Wroblewski, Victor J
Hellewell, Paul G
Whyte, Moira K B
Dockrell, David H
author_facet Marriott, Helen M
Daigneault, Marc
Thompson, Alfred A R
Walmsley, Sarah R
Gill, Sharonjit K
Witcher, Derrick R
Wroblewski, Victor J
Hellewell, Paul G
Whyte, Moira K B
Dockrell, David H
author_sort Marriott, Helen M
collection PubMed
description BACKGROUND: Therapeutic strategies to modulate the host response to bacterial pneumonia are needed to improve outcomes during community-acquired pneumonia. This study used mice with impaired Fas signalling to examine susceptibility to pneumococcal pneumonia and decoy receptor 3 analogue (DcR3-a) to correct factors associated with increased susceptibility. METHODS: Wild-type mice and those with varying degrees of impairment of Fas (lpr) or Fas ligand signalling (gld) were challenged with Streptococcus pneumoniae and microbiological and immunological outcomes measured in the presence or absence of DcR3-a. RESULTS: During established pneumonia, neutrophils became the predominant cell in the airway and gld mice were less able to clear bacteria from the lungs, demonstrating localised impairment of pulmonary neutrophil function in comparison to lpr or wild-type mice. T-cells from gld mice had enhanced activation and reduced apoptosis in comparison to wild-type and lpr mice during established pneumonia. Treatment with DcR3-a reduced T-cell activation and corrected the defect in pulmonary bacterial clearance in gld mice. CONCLUSIONS: The results suggest that imbalance in tumour necrosis factor superfamily signalling and excessive T-cell activation can impair bacterial clearance in the lung but that DcR3-a treatment can reduce T-cell activation, restore optimal pulmonary neutrophil function and enhance bacterial clearance during S pneumoniae infection.
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spelling pubmed-35058692012-11-26 A decoy receptor 3 analogue reduces localised defects in phagocyte function in pneumococcal pneumonia Marriott, Helen M Daigneault, Marc Thompson, Alfred A R Walmsley, Sarah R Gill, Sharonjit K Witcher, Derrick R Wroblewski, Victor J Hellewell, Paul G Whyte, Moira K B Dockrell, David H Thorax Original Articles BACKGROUND: Therapeutic strategies to modulate the host response to bacterial pneumonia are needed to improve outcomes during community-acquired pneumonia. This study used mice with impaired Fas signalling to examine susceptibility to pneumococcal pneumonia and decoy receptor 3 analogue (DcR3-a) to correct factors associated with increased susceptibility. METHODS: Wild-type mice and those with varying degrees of impairment of Fas (lpr) or Fas ligand signalling (gld) were challenged with Streptococcus pneumoniae and microbiological and immunological outcomes measured in the presence or absence of DcR3-a. RESULTS: During established pneumonia, neutrophils became the predominant cell in the airway and gld mice were less able to clear bacteria from the lungs, demonstrating localised impairment of pulmonary neutrophil function in comparison to lpr or wild-type mice. T-cells from gld mice had enhanced activation and reduced apoptosis in comparison to wild-type and lpr mice during established pneumonia. Treatment with DcR3-a reduced T-cell activation and corrected the defect in pulmonary bacterial clearance in gld mice. CONCLUSIONS: The results suggest that imbalance in tumour necrosis factor superfamily signalling and excessive T-cell activation can impair bacterial clearance in the lung but that DcR3-a treatment can reduce T-cell activation, restore optimal pulmonary neutrophil function and enhance bacterial clearance during S pneumoniae infection. BMJ Group 2012-11 2012-06-26 /pmc/articles/PMC3505869/ /pubmed/22735687 http://dx.doi.org/10.1136/thoraxjnl-2012-201591 Text en Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions This is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the license. See: http://creativecommons.org/licenses/by-nc/2.0/ and http://creativecommons.org/licenses/by-nc/2.0/legalcode.
spellingShingle Original Articles
Marriott, Helen M
Daigneault, Marc
Thompson, Alfred A R
Walmsley, Sarah R
Gill, Sharonjit K
Witcher, Derrick R
Wroblewski, Victor J
Hellewell, Paul G
Whyte, Moira K B
Dockrell, David H
A decoy receptor 3 analogue reduces localised defects in phagocyte function in pneumococcal pneumonia
title A decoy receptor 3 analogue reduces localised defects in phagocyte function in pneumococcal pneumonia
title_full A decoy receptor 3 analogue reduces localised defects in phagocyte function in pneumococcal pneumonia
title_fullStr A decoy receptor 3 analogue reduces localised defects in phagocyte function in pneumococcal pneumonia
title_full_unstemmed A decoy receptor 3 analogue reduces localised defects in phagocyte function in pneumococcal pneumonia
title_short A decoy receptor 3 analogue reduces localised defects in phagocyte function in pneumococcal pneumonia
title_sort decoy receptor 3 analogue reduces localised defects in phagocyte function in pneumococcal pneumonia
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3505869/
https://www.ncbi.nlm.nih.gov/pubmed/22735687
http://dx.doi.org/10.1136/thoraxjnl-2012-201591
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