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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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Autores principales: Barat, Somedutta, Willer, Yvonne, Rizos, Konstantin, Claudi, Beatrice, Mazé, Alain, Schemmer, Anne K., Kirchhoff, Dennis, Schmidt, Alexander, Burton, Neil, Bumann, Dirk
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3475680/
https://www.ncbi.nlm.nih.gov/pubmed/23093937
http://dx.doi.org/10.1371/journal.ppat.1002966
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author Barat, Somedutta
Willer, Yvonne
Rizos, Konstantin
Claudi, Beatrice
Mazé, Alain
Schemmer, Anne K.
Kirchhoff, Dennis
Schmidt, Alexander
Burton, Neil
Bumann, Dirk
author_facet Barat, Somedutta
Willer, Yvonne
Rizos, Konstantin
Claudi, Beatrice
Mazé, Alain
Schemmer, Anne K.
Kirchhoff, Dennis
Schmidt, Alexander
Burton, Neil
Bumann, Dirk
author_sort Barat, Somedutta
collection PubMed
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.
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spelling pubmed-34756802012-10-23 Immunity to Intracellular Salmonella Depends on Surface-associated Antigens Barat, Somedutta Willer, Yvonne Rizos, Konstantin Claudi, Beatrice Mazé, Alain Schemmer, Anne K. Kirchhoff, Dennis Schmidt, Alexander Burton, Neil Bumann, Dirk PLoS Pathog Research Article 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. Public Library of Science 2012-10-18 /pmc/articles/PMC3475680/ /pubmed/23093937 http://dx.doi.org/10.1371/journal.ppat.1002966 Text en © 2012 Barat 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, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Barat, Somedutta
Willer, Yvonne
Rizos, Konstantin
Claudi, Beatrice
Mazé, Alain
Schemmer, Anne K.
Kirchhoff, Dennis
Schmidt, Alexander
Burton, Neil
Bumann, Dirk
Immunity to Intracellular Salmonella Depends on Surface-associated Antigens
title 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_short Immunity to Intracellular Salmonella Depends on Surface-associated Antigens
title_sort immunity to intracellular salmonella depends on surface-associated antigens
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3475680/
https://www.ncbi.nlm.nih.gov/pubmed/23093937
http://dx.doi.org/10.1371/journal.ppat.1002966
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