Cargando…
Combinatorial processing of bacterial and host-derived innate immune stimuli at the single-cell level
During the course of a bacterial infection, cells are exposed simultaneously to a range of bacterial and host factors, which converge on the central transcription factor nuclear factor (NF)-κB. How do single cells integrate and process these converging stimuli? Here we tackle the question of how cel...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6589564/ https://www.ncbi.nlm.nih.gov/pubmed/30462580 http://dx.doi.org/10.1091/mbc.E18-07-0423 |
_version_ | 1783429410797387776 |
---|---|
author | Gutschow, Miriam V. Mason, John C. Lane, Keara M. Maayan, Inbal Hughey, Jacob J. Bajar, Bryce T. Amatya, Debha N. Valle, Sean D. Covert, Markus W. |
author_facet | Gutschow, Miriam V. Mason, John C. Lane, Keara M. Maayan, Inbal Hughey, Jacob J. Bajar, Bryce T. Amatya, Debha N. Valle, Sean D. Covert, Markus W. |
author_sort | Gutschow, Miriam V. |
collection | PubMed |
description | During the course of a bacterial infection, cells are exposed simultaneously to a range of bacterial and host factors, which converge on the central transcription factor nuclear factor (NF)-κB. How do single cells integrate and process these converging stimuli? Here we tackle the question of how cells process combinatorial signals by making quantitative single-cell measurements of the NF-κB response to combinations of bacterial lipopolysaccharide and the stress cytokine tumor necrosis factor. We found that cells encode the presence of both stimuli via the dynamics of NF-κB nuclear translocation in individual cells, suggesting the integration of NF-κB activity for these stimuli occurs at the molecular and pathway level. However, the gene expression and cytokine secretion response to combinatorial stimuli were more complex, suggesting that other factors in addition to NF-κB contribute to signal integration at downstream layers of the response. Taken together, our results support the theory that during innate immune threat assessment, a pathogen recognized as both foreign and harmful will recruit an enhanced immune response. Our work highlights the remarkable capacity of individual cells to process multiple input signals and suggests that a deeper understanding of signal integration mechanisms will facilitate efforts to control dysregulated immune responses. |
format | Online Article Text |
id | pubmed-6589564 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-65895642019-06-28 Combinatorial processing of bacterial and host-derived innate immune stimuli at the single-cell level Gutschow, Miriam V. Mason, John C. Lane, Keara M. Maayan, Inbal Hughey, Jacob J. Bajar, Bryce T. Amatya, Debha N. Valle, Sean D. Covert, Markus W. Mol Biol Cell Articles During the course of a bacterial infection, cells are exposed simultaneously to a range of bacterial and host factors, which converge on the central transcription factor nuclear factor (NF)-κB. How do single cells integrate and process these converging stimuli? Here we tackle the question of how cells process combinatorial signals by making quantitative single-cell measurements of the NF-κB response to combinations of bacterial lipopolysaccharide and the stress cytokine tumor necrosis factor. We found that cells encode the presence of both stimuli via the dynamics of NF-κB nuclear translocation in individual cells, suggesting the integration of NF-κB activity for these stimuli occurs at the molecular and pathway level. However, the gene expression and cytokine secretion response to combinatorial stimuli were more complex, suggesting that other factors in addition to NF-κB contribute to signal integration at downstream layers of the response. Taken together, our results support the theory that during innate immune threat assessment, a pathogen recognized as both foreign and harmful will recruit an enhanced immune response. Our work highlights the remarkable capacity of individual cells to process multiple input signals and suggests that a deeper understanding of signal integration mechanisms will facilitate efforts to control dysregulated immune responses. The American Society for Cell Biology 2019-01-15 /pmc/articles/PMC6589564/ /pubmed/30462580 http://dx.doi.org/10.1091/mbc.E18-07-0423 Text en © 2019 Gutschow et al. “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology. http://creativecommons.org/licenses/by-nc-sa/3.0 This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License. |
spellingShingle | Articles Gutschow, Miriam V. Mason, John C. Lane, Keara M. Maayan, Inbal Hughey, Jacob J. Bajar, Bryce T. Amatya, Debha N. Valle, Sean D. Covert, Markus W. Combinatorial processing of bacterial and host-derived innate immune stimuli at the single-cell level |
title | Combinatorial processing of bacterial and host-derived innate immune stimuli at the single-cell level |
title_full | Combinatorial processing of bacterial and host-derived innate immune stimuli at the single-cell level |
title_fullStr | Combinatorial processing of bacterial and host-derived innate immune stimuli at the single-cell level |
title_full_unstemmed | Combinatorial processing of bacterial and host-derived innate immune stimuli at the single-cell level |
title_short | Combinatorial processing of bacterial and host-derived innate immune stimuli at the single-cell level |
title_sort | combinatorial processing of bacterial and host-derived innate immune stimuli at the single-cell level |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6589564/ https://www.ncbi.nlm.nih.gov/pubmed/30462580 http://dx.doi.org/10.1091/mbc.E18-07-0423 |
work_keys_str_mv | AT gutschowmiriamv combinatorialprocessingofbacterialandhostderivedinnateimmunestimuliatthesinglecelllevel AT masonjohnc combinatorialprocessingofbacterialandhostderivedinnateimmunestimuliatthesinglecelllevel AT lanekearam combinatorialprocessingofbacterialandhostderivedinnateimmunestimuliatthesinglecelllevel AT maayaninbal combinatorialprocessingofbacterialandhostderivedinnateimmunestimuliatthesinglecelllevel AT hugheyjacobj combinatorialprocessingofbacterialandhostderivedinnateimmunestimuliatthesinglecelllevel AT bajarbrycet combinatorialprocessingofbacterialandhostderivedinnateimmunestimuliatthesinglecelllevel AT amatyadebhan combinatorialprocessingofbacterialandhostderivedinnateimmunestimuliatthesinglecelllevel AT valleseand combinatorialprocessingofbacterialandhostderivedinnateimmunestimuliatthesinglecelllevel AT covertmarkusw combinatorialprocessingofbacterialandhostderivedinnateimmunestimuliatthesinglecelllevel |