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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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Microbiology
2019
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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. |
format | Online Article Text |
id | pubmed-6315100 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | American Society for Microbiology |
record_format | MEDLINE/PubMed |
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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