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Differential Killing of Salmonella enterica Serovar Typhi by Antibodies Targeting Vi and Lipopolysaccharide O:9 Antigen
Salmonella enterica serovar Typhi expresses a capsule of Vi polysaccharide, while most Salmonella serovars, including S. Enteritidis and S. Typhimurium, do not. Both S. Typhi and S. Enteritidis express the lipopolysaccharide O:9 antigen, yet there is little evidence of cross-protection from anti-O:9...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4712142/ https://www.ncbi.nlm.nih.gov/pubmed/26741681 http://dx.doi.org/10.1371/journal.pone.0145945 |
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author | Hart, Peter J. O’Shaughnessy, Colette M. Siggins, Matthew K. Bobat, Saeeda Kingsley, Robert A. Goulding, David A. Crump, John A. Reyburn, Hugh Micoli, Francesca Dougan, Gordon Cunningham, Adam F. MacLennan, Calman A. |
author_facet | Hart, Peter J. O’Shaughnessy, Colette M. Siggins, Matthew K. Bobat, Saeeda Kingsley, Robert A. Goulding, David A. Crump, John A. Reyburn, Hugh Micoli, Francesca Dougan, Gordon Cunningham, Adam F. MacLennan, Calman A. |
author_sort | Hart, Peter J. |
collection | PubMed |
description | Salmonella enterica serovar Typhi expresses a capsule of Vi polysaccharide, while most Salmonella serovars, including S. Enteritidis and S. Typhimurium, do not. Both S. Typhi and S. Enteritidis express the lipopolysaccharide O:9 antigen, yet there is little evidence of cross-protection from anti-O:9 antibodies. Vaccines based on Vi polysaccharide have efficacy against typhoid fever, indicating that antibodies against Vi confer protection. Here we investigate the role of Vi capsule and antibodies against Vi and O:9 in antibody-dependent complement- and phagocyte-mediated killing of Salmonella. Using isogenic Vi-expressing and non-Vi-expressing derivatives of S. Typhi and S. Typhimurium, we show that S. Typhi is inherently more sensitive to serum and blood than S. Typhimurium. Vi expression confers increased resistance to both complement- and phagocyte-mediated modalities of antibody-dependent killing in human blood. The Vi capsule is associated with reduced C3 and C5b-9 deposition, and decreased overall antibody binding to S. Typhi. However, purified human anti-Vi antibodies in the presence of complement are able to kill Vi-expressing Salmonella, while killing by anti-O:9 antibodies is inversely related to Vi expression. Human serum depleted of antibodies to antigens other than Vi retains the ability to kill Vi-expressing bacteria. Our findings support a protective role for Vi capsule in preventing complement and phagocyte killing of Salmonella that can be overcome by specific anti-Vi antibodies, but only to a limited extent by anti-O:9 antibodies. |
format | Online Article Text |
id | pubmed-4712142 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-47121422016-01-26 Differential Killing of Salmonella enterica Serovar Typhi by Antibodies Targeting Vi and Lipopolysaccharide O:9 Antigen Hart, Peter J. O’Shaughnessy, Colette M. Siggins, Matthew K. Bobat, Saeeda Kingsley, Robert A. Goulding, David A. Crump, John A. Reyburn, Hugh Micoli, Francesca Dougan, Gordon Cunningham, Adam F. MacLennan, Calman A. PLoS One Research Article Salmonella enterica serovar Typhi expresses a capsule of Vi polysaccharide, while most Salmonella serovars, including S. Enteritidis and S. Typhimurium, do not. Both S. Typhi and S. Enteritidis express the lipopolysaccharide O:9 antigen, yet there is little evidence of cross-protection from anti-O:9 antibodies. Vaccines based on Vi polysaccharide have efficacy against typhoid fever, indicating that antibodies against Vi confer protection. Here we investigate the role of Vi capsule and antibodies against Vi and O:9 in antibody-dependent complement- and phagocyte-mediated killing of Salmonella. Using isogenic Vi-expressing and non-Vi-expressing derivatives of S. Typhi and S. Typhimurium, we show that S. Typhi is inherently more sensitive to serum and blood than S. Typhimurium. Vi expression confers increased resistance to both complement- and phagocyte-mediated modalities of antibody-dependent killing in human blood. The Vi capsule is associated with reduced C3 and C5b-9 deposition, and decreased overall antibody binding to S. Typhi. However, purified human anti-Vi antibodies in the presence of complement are able to kill Vi-expressing Salmonella, while killing by anti-O:9 antibodies is inversely related to Vi expression. Human serum depleted of antibodies to antigens other than Vi retains the ability to kill Vi-expressing bacteria. Our findings support a protective role for Vi capsule in preventing complement and phagocyte killing of Salmonella that can be overcome by specific anti-Vi antibodies, but only to a limited extent by anti-O:9 antibodies. Public Library of Science 2016-01-07 /pmc/articles/PMC4712142/ /pubmed/26741681 http://dx.doi.org/10.1371/journal.pone.0145945 Text en © 2016 Hart 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 (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited |
spellingShingle | Research Article Hart, Peter J. O’Shaughnessy, Colette M. Siggins, Matthew K. Bobat, Saeeda Kingsley, Robert A. Goulding, David A. Crump, John A. Reyburn, Hugh Micoli, Francesca Dougan, Gordon Cunningham, Adam F. MacLennan, Calman A. Differential Killing of Salmonella enterica Serovar Typhi by Antibodies Targeting Vi and Lipopolysaccharide O:9 Antigen |
title | Differential Killing of Salmonella enterica Serovar Typhi by Antibodies Targeting Vi and Lipopolysaccharide O:9 Antigen |
title_full | Differential Killing of Salmonella enterica Serovar Typhi by Antibodies Targeting Vi and Lipopolysaccharide O:9 Antigen |
title_fullStr | Differential Killing of Salmonella enterica Serovar Typhi by Antibodies Targeting Vi and Lipopolysaccharide O:9 Antigen |
title_full_unstemmed | Differential Killing of Salmonella enterica Serovar Typhi by Antibodies Targeting Vi and Lipopolysaccharide O:9 Antigen |
title_short | Differential Killing of Salmonella enterica Serovar Typhi by Antibodies Targeting Vi and Lipopolysaccharide O:9 Antigen |
title_sort | differential killing of salmonella enterica serovar typhi by antibodies targeting vi and lipopolysaccharide o:9 antigen |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4712142/ https://www.ncbi.nlm.nih.gov/pubmed/26741681 http://dx.doi.org/10.1371/journal.pone.0145945 |
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