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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Main Authors: Somedutta Barat, Yvonne Willer, Konstantin Rizos, Beatrice Claudi, Alain Mazé, Anne K Schemmer, Dennis Kirchhoff, Alexander Schmidt, Neil Burton, Dirk Bumann
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2012-01-01
Series:PLoS Pathogens
Online Access:http://europepmc.org/articles/PMC3475680?pdf=render
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spelling 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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