Immunity to intracellular Salmonella depends on surface-associated antigens.
Invasive Salmonella infection is an important health problem that is worsening because of rising antimicrobial resistance and changing Salmonella serovar spectrum. Novel vaccines with broad serovar coverage are needed, but suitable protective antigens remain largely unknown. Here, we tested 37 broad...
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2012-01-01
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doaj-896b33ce87dc41e19002c8e71a86899a2020-11-25T00:09:53ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742012-01-01810e100296610.1371/journal.ppat.1002966Immunity to intracellular Salmonella depends on surface-associated antigens.Somedutta BaratYvonne WillerKonstantin RizosBeatrice ClaudiAlain MazéAnne K SchemmerDennis KirchhoffAlexander SchmidtNeil BurtonDirk BumannInvasive Salmonella infection is an important health problem that is worsening because of rising antimicrobial resistance and changing Salmonella serovar spectrum. Novel vaccines with broad serovar coverage are needed, but suitable protective antigens remain largely unknown. Here, we tested 37 broadly conserved Salmonella antigens in a mouse typhoid fever model, and identified antigen candidates that conferred partial protection against lethal disease. Antigen properties such as high in vivo abundance or immunodominance in convalescent individuals were not required for protectivity, but all promising antigen candidates were associated with the Salmonella surface. Surprisingly, this was not due to superior immunogenicity of surface antigens compared to internal antigens as had been suggested by previous studies and novel findings for CD4 T cell responses to model antigens. Confocal microscopy of infected tissues revealed that many live Salmonella resided alone in infected host macrophages with no damaged Salmonella releasing internal antigens in their vicinity. In the absence of accessible internal antigens, detection of these infected cells might require CD4 T cell recognition of Salmonella surface-associated antigens that could be processed and presented even from intact Salmonella. In conclusion, our findings might pave the way for development of an efficacious Salmonella vaccine with broad serovar coverage, and suggest a similar crucial role of surface antigens for immunity to both extracellular and intracellular pathogens.http://europepmc.org/articles/PMC3475680?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Somedutta Barat Yvonne Willer Konstantin Rizos Beatrice Claudi Alain Mazé Anne K Schemmer Dennis Kirchhoff Alexander Schmidt Neil Burton Dirk Bumann |
spellingShingle |
Somedutta Barat Yvonne Willer Konstantin Rizos Beatrice Claudi Alain Mazé Anne K Schemmer Dennis Kirchhoff Alexander Schmidt Neil Burton Dirk Bumann Immunity to intracellular Salmonella depends on surface-associated antigens. PLoS Pathogens |
author_facet |
Somedutta Barat Yvonne Willer Konstantin Rizos Beatrice Claudi Alain Mazé Anne K Schemmer Dennis Kirchhoff Alexander Schmidt Neil Burton Dirk Bumann |
author_sort |
Somedutta Barat |
title |
Immunity to intracellular Salmonella depends on surface-associated antigens. |
title_short |
Immunity to intracellular Salmonella depends on surface-associated antigens. |
title_full |
Immunity to intracellular Salmonella depends on surface-associated antigens. |
title_fullStr |
Immunity to intracellular Salmonella depends on surface-associated antigens. |
title_full_unstemmed |
Immunity to intracellular Salmonella depends on surface-associated antigens. |
title_sort |
immunity to intracellular salmonella depends on surface-associated antigens. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS Pathogens |
issn |
1553-7366 1553-7374 |
publishDate |
2012-01-01 |
description |
Invasive Salmonella infection is an important health problem that is worsening because of rising antimicrobial resistance and changing Salmonella serovar spectrum. Novel vaccines with broad serovar coverage are needed, but suitable protective antigens remain largely unknown. Here, we tested 37 broadly conserved Salmonella antigens in a mouse typhoid fever model, and identified antigen candidates that conferred partial protection against lethal disease. Antigen properties such as high in vivo abundance or immunodominance in convalescent individuals were not required for protectivity, but all promising antigen candidates were associated with the Salmonella surface. Surprisingly, this was not due to superior immunogenicity of surface antigens compared to internal antigens as had been suggested by previous studies and novel findings for CD4 T cell responses to model antigens. Confocal microscopy of infected tissues revealed that many live Salmonella resided alone in infected host macrophages with no damaged Salmonella releasing internal antigens in their vicinity. In the absence of accessible internal antigens, detection of these infected cells might require CD4 T cell recognition of Salmonella surface-associated antigens that could be processed and presented even from intact Salmonella. In conclusion, our findings might pave the way for development of an efficacious Salmonella vaccine with broad serovar coverage, and suggest a similar crucial role of surface antigens for immunity to both extracellular and intracellular pathogens. |
url |
http://europepmc.org/articles/PMC3475680?pdf=render |
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