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Vaccine-induced inflammation and inflammatory monocytes promote CD4(+) T cell-dependent immunity against murine salmonellosis

Prior infection can generate protective immunity against subsequent infection, although the efficacy of such immunity can vary considerably. Live-attenuated vaccines (LAVs) are one of the most effective methods for mimicking this natural process, and analysis of their efficacy has proven instrumenta...

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Autores principales: Wang, Nancy, Scott, Timothy A., Kupz, Andreas, Shreenivas, Meghanashree M., Peres, Newton G., Hocking, Dianna M., Yang, Chenying, Jebeli, Leila, Beattie, Lynette, Groom, Joanna R., Pierce, Thomas P., Wakim, Linda M., Bedoui, Sammy, Strugnell, Richard A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10547166/
https://www.ncbi.nlm.nih.gov/pubmed/37733817
http://dx.doi.org/10.1371/journal.ppat.1011666
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author Wang, Nancy
Scott, Timothy A.
Kupz, Andreas
Shreenivas, Meghanashree M.
Peres, Newton G.
Hocking, Dianna M.
Yang, Chenying
Jebeli, Leila
Beattie, Lynette
Groom, Joanna R.
Pierce, Thomas P.
Wakim, Linda M.
Bedoui, Sammy
Strugnell, Richard A.
author_facet Wang, Nancy
Scott, Timothy A.
Kupz, Andreas
Shreenivas, Meghanashree M.
Peres, Newton G.
Hocking, Dianna M.
Yang, Chenying
Jebeli, Leila
Beattie, Lynette
Groom, Joanna R.
Pierce, Thomas P.
Wakim, Linda M.
Bedoui, Sammy
Strugnell, Richard A.
author_sort Wang, Nancy
collection PubMed
description Prior infection can generate protective immunity against subsequent infection, although the efficacy of such immunity can vary considerably. Live-attenuated vaccines (LAVs) are one of the most effective methods for mimicking this natural process, and analysis of their efficacy has proven instrumental in the identification of protective immune mechanisms. Here, we address the question of what makes a LAV efficacious by characterising immune responses to a LAV, termed TAS2010, which is highly protective (80–90%) against lethal murine salmonellosis, in comparison with a moderately protective (40–50%) LAV, BRD509. Mice vaccinated with TAS2010 developed immunity systemically and were protected against gut-associated virulent infection in a CD4(+) T cell-dependent manner. TAS2010-vaccinated mice showed increased activation of Th1 responses compared with their BRD509-vaccinated counterparts, leading to increased Th1 memory populations in both lymphoid and non-lymphoid organs. The optimal development of Th1-driven immunity was closely correlated with the activation of CD11b(+)Ly6G(neg)Ly6C(hi) inflammatory monocytes (IMs), the activation of which can be modulated proportionally by bacterial load in vivo. Upon vaccination with the LAV, IMs expressed T cell chemoattractant CXCL9 that attracted CD4(+) T cells to the foci of infection, where IMs also served as a potent source of antigen presentation and Th1-promoting cytokine IL-12. The expression of MHC-II in IMs was rapidly upregulated following vaccination and then maintained at an elevated level in immune mice, suggesting IMs may have a role in sustained antigen stimulation. Our findings present a longitudinal analysis of CD4(+) T cell development post-vaccination with an intracellular bacterial LAV, and highlight the benefit of inflammation in the development of Th1 immunity. Future studies focusing on the induction of IMs may reveal key strategies for improving vaccine-induced T cell immunity.
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spelling pubmed-105471662023-10-04 Vaccine-induced inflammation and inflammatory monocytes promote CD4(+) T cell-dependent immunity against murine salmonellosis Wang, Nancy Scott, Timothy A. Kupz, Andreas Shreenivas, Meghanashree M. Peres, Newton G. Hocking, Dianna M. Yang, Chenying Jebeli, Leila Beattie, Lynette Groom, Joanna R. Pierce, Thomas P. Wakim, Linda M. Bedoui, Sammy Strugnell, Richard A. PLoS Pathog Research Article Prior infection can generate protective immunity against subsequent infection, although the efficacy of such immunity can vary considerably. Live-attenuated vaccines (LAVs) are one of the most effective methods for mimicking this natural process, and analysis of their efficacy has proven instrumental in the identification of protective immune mechanisms. Here, we address the question of what makes a LAV efficacious by characterising immune responses to a LAV, termed TAS2010, which is highly protective (80–90%) against lethal murine salmonellosis, in comparison with a moderately protective (40–50%) LAV, BRD509. Mice vaccinated with TAS2010 developed immunity systemically and were protected against gut-associated virulent infection in a CD4(+) T cell-dependent manner. TAS2010-vaccinated mice showed increased activation of Th1 responses compared with their BRD509-vaccinated counterparts, leading to increased Th1 memory populations in both lymphoid and non-lymphoid organs. The optimal development of Th1-driven immunity was closely correlated with the activation of CD11b(+)Ly6G(neg)Ly6C(hi) inflammatory monocytes (IMs), the activation of which can be modulated proportionally by bacterial load in vivo. Upon vaccination with the LAV, IMs expressed T cell chemoattractant CXCL9 that attracted CD4(+) T cells to the foci of infection, where IMs also served as a potent source of antigen presentation and Th1-promoting cytokine IL-12. The expression of MHC-II in IMs was rapidly upregulated following vaccination and then maintained at an elevated level in immune mice, suggesting IMs may have a role in sustained antigen stimulation. Our findings present a longitudinal analysis of CD4(+) T cell development post-vaccination with an intracellular bacterial LAV, and highlight the benefit of inflammation in the development of Th1 immunity. Future studies focusing on the induction of IMs may reveal key strategies for improving vaccine-induced T cell immunity. Public Library of Science 2023-09-21 /pmc/articles/PMC10547166/ /pubmed/37733817 http://dx.doi.org/10.1371/journal.ppat.1011666 Text en © 2023 Wang et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://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
Wang, Nancy
Scott, Timothy A.
Kupz, Andreas
Shreenivas, Meghanashree M.
Peres, Newton G.
Hocking, Dianna M.
Yang, Chenying
Jebeli, Leila
Beattie, Lynette
Groom, Joanna R.
Pierce, Thomas P.
Wakim, Linda M.
Bedoui, Sammy
Strugnell, Richard A.
Vaccine-induced inflammation and inflammatory monocytes promote CD4(+) T cell-dependent immunity against murine salmonellosis
title Vaccine-induced inflammation and inflammatory monocytes promote CD4(+) T cell-dependent immunity against murine salmonellosis
title_full Vaccine-induced inflammation and inflammatory monocytes promote CD4(+) T cell-dependent immunity against murine salmonellosis
title_fullStr Vaccine-induced inflammation and inflammatory monocytes promote CD4(+) T cell-dependent immunity against murine salmonellosis
title_full_unstemmed Vaccine-induced inflammation and inflammatory monocytes promote CD4(+) T cell-dependent immunity against murine salmonellosis
title_short Vaccine-induced inflammation and inflammatory monocytes promote CD4(+) T cell-dependent immunity against murine salmonellosis
title_sort vaccine-induced inflammation and inflammatory monocytes promote cd4(+) t cell-dependent immunity against murine salmonellosis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10547166/
https://www.ncbi.nlm.nih.gov/pubmed/37733817
http://dx.doi.org/10.1371/journal.ppat.1011666
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