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Staphylococcus aureus Impairs the Function of and Kills Human Dendritic Cells via the LukAB Toxin

Staphylococcus aureus is a human pathogen responsible for high morbidity and mortality worldwide. Recurrent infections with this bacterium are common, suggesting that S. aureus thwarts the development of sterilizing immunity. S. aureus strains that cause disease in humans produce up to five differen...

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Autores principales: Berends, Evelien T. M., Zheng, Xuhui, Zwack, Erin E., Ménager, Mickaël M., Cammer, Michael, Shopsin, Bo, Torres, Victor J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6315100/
https://www.ncbi.nlm.nih.gov/pubmed/30602580
http://dx.doi.org/10.1128/mBio.01918-18
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author Berends, Evelien T. M.
Zheng, Xuhui
Zwack, Erin E.
Ménager, Mickaël M.
Cammer, Michael
Shopsin, Bo
Torres, Victor J.
author_facet Berends, Evelien T. M.
Zheng, Xuhui
Zwack, Erin E.
Ménager, Mickaël M.
Cammer, Michael
Shopsin, Bo
Torres, Victor J.
author_sort Berends, Evelien T. M.
collection PubMed
description Staphylococcus aureus is a human pathogen responsible for high morbidity and mortality worldwide. Recurrent infections with this bacterium are common, suggesting that S. aureus thwarts the development of sterilizing immunity. S. aureus strains that cause disease in humans produce up to five different bicomponent toxins (leukocidins) that target and lyse neutrophils, innate immune cells that represent the first line of defense against S. aureus infections. However, little is known about the role of leukocidins in blunting adaptive immunity. Here, we explored the effects of leukocidins on human dendritic cells (DCs), antigen-presenting cells required for the development of adaptive immunity. Using an ex vivo infection model of primary human monocyte-derived dendritic cells, we found that S. aureus, including strains from different clonal complexes and drug resistance profiles, effectively kills DCs despite efficient phagocytosis. Although all purified leukocidins could kill DCs, infections with live bacteria revealed that S. aureus targets and kills DCs primarily via the activity of leukocidin LukAB. Moreover, using coculture experiments performed with DCs and autologous CD4(+) T lymphocytes, we found that LukAB inhibits DC-mediated activation and proliferation of primary human T cells. Taken together, the data determined in the study reveal a novel immunosuppressive strategy of S. aureus whereby the bacterium blunts the development of adaptive immunity via LukAB-mediated injury of DCs.
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spelling pubmed-63151002019-01-11 Staphylococcus aureus Impairs the Function of and Kills Human Dendritic Cells via the LukAB Toxin Berends, Evelien T. M. Zheng, Xuhui Zwack, Erin E. Ménager, Mickaël M. Cammer, Michael Shopsin, Bo Torres, Victor J. mBio Research Article Staphylococcus aureus is a human pathogen responsible for high morbidity and mortality worldwide. Recurrent infections with this bacterium are common, suggesting that S. aureus thwarts the development of sterilizing immunity. S. aureus strains that cause disease in humans produce up to five different bicomponent toxins (leukocidins) that target and lyse neutrophils, innate immune cells that represent the first line of defense against S. aureus infections. However, little is known about the role of leukocidins in blunting adaptive immunity. Here, we explored the effects of leukocidins on human dendritic cells (DCs), antigen-presenting cells required for the development of adaptive immunity. Using an ex vivo infection model of primary human monocyte-derived dendritic cells, we found that S. aureus, including strains from different clonal complexes and drug resistance profiles, effectively kills DCs despite efficient phagocytosis. Although all purified leukocidins could kill DCs, infections with live bacteria revealed that S. aureus targets and kills DCs primarily via the activity of leukocidin LukAB. Moreover, using coculture experiments performed with DCs and autologous CD4(+) T lymphocytes, we found that LukAB inhibits DC-mediated activation and proliferation of primary human T cells. Taken together, the data determined in the study reveal a novel immunosuppressive strategy of S. aureus whereby the bacterium blunts the development of adaptive immunity via LukAB-mediated injury of DCs. American Society for Microbiology 2019-01-02 /pmc/articles/PMC6315100/ /pubmed/30602580 http://dx.doi.org/10.1128/mBio.01918-18 Text en Copyright © 2019 Berends et al. https://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Berends, Evelien T. M.
Zheng, Xuhui
Zwack, Erin E.
Ménager, Mickaël M.
Cammer, Michael
Shopsin, Bo
Torres, Victor J.
Staphylococcus aureus Impairs the Function of and Kills Human Dendritic Cells via the LukAB Toxin
title Staphylococcus aureus Impairs the Function of and Kills Human Dendritic Cells via the LukAB Toxin
title_full Staphylococcus aureus Impairs the Function of and Kills Human Dendritic Cells via the LukAB Toxin
title_fullStr Staphylococcus aureus Impairs the Function of and Kills Human Dendritic Cells via the LukAB Toxin
title_full_unstemmed Staphylococcus aureus Impairs the Function of and Kills Human Dendritic Cells via the LukAB Toxin
title_short Staphylococcus aureus Impairs the Function of and Kills Human Dendritic Cells via the LukAB Toxin
title_sort staphylococcus aureus impairs the function of and kills human dendritic cells via the lukab toxin
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6315100/
https://www.ncbi.nlm.nih.gov/pubmed/30602580
http://dx.doi.org/10.1128/mBio.01918-18
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