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Antigen discovery unveils resident memory and migratory cell roles in antifungal resistance
Priming at the site of natural infection typically elicits a protective T cell response against subsequent pathogen encounter. Here, we report the identification of a novel fungal antigen that we harnessed for mucosal vaccination and tetramer generation to test whether we can elicit protective, anti...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7183437/ https://www.ncbi.nlm.nih.gov/pubmed/31900406 http://dx.doi.org/10.1038/s41385-019-0244-3 |
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author | Dobson, Hannah E. Dias, Lucas Dos Santos Kohn, Elaine M. Fites, Scott Wiesner, Darin L. Dileepan, Thamotharampillai Kujoth, Gregory C. Abraham, Ambily Ostroff, Gary R. Klein, Bruce S. Wüthrich, Marcel |
author_facet | Dobson, Hannah E. Dias, Lucas Dos Santos Kohn, Elaine M. Fites, Scott Wiesner, Darin L. Dileepan, Thamotharampillai Kujoth, Gregory C. Abraham, Ambily Ostroff, Gary R. Klein, Bruce S. Wüthrich, Marcel |
author_sort | Dobson, Hannah E. |
collection | PubMed |
description | Priming at the site of natural infection typically elicits a protective T cell response against subsequent pathogen encounter. Here, we report the identification of a novel fungal antigen that we harnessed for mucosal vaccination and tetramer generation to test whether we can elicit protective, antigen-specific tissue resident memory (Trm) CD4(+) T cells in the lung parenchyma. In contrast to expectations, CD69(+), CXCR3(+), CD103(−) Trm cells failed to protect against a lethal pulmonary fungal infection. Surprisingly, systemic vaccination induced a population of tetramer(+) CD4(+) T cells enriched within the pulmonary vasculature, and expressing CXCR3 and CX3CR1, that migrated to the lung tissue upon challenge and efficiently protected mice against infection. Mucosal vaccine priming of Trm may not reliably protect against mucosal pathogens. |
format | Online Article Text |
id | pubmed-7183437 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
record_format | MEDLINE/PubMed |
spelling | pubmed-71834372020-07-03 Antigen discovery unveils resident memory and migratory cell roles in antifungal resistance Dobson, Hannah E. Dias, Lucas Dos Santos Kohn, Elaine M. Fites, Scott Wiesner, Darin L. Dileepan, Thamotharampillai Kujoth, Gregory C. Abraham, Ambily Ostroff, Gary R. Klein, Bruce S. Wüthrich, Marcel Mucosal Immunol Article Priming at the site of natural infection typically elicits a protective T cell response against subsequent pathogen encounter. Here, we report the identification of a novel fungal antigen that we harnessed for mucosal vaccination and tetramer generation to test whether we can elicit protective, antigen-specific tissue resident memory (Trm) CD4(+) T cells in the lung parenchyma. In contrast to expectations, CD69(+), CXCR3(+), CD103(−) Trm cells failed to protect against a lethal pulmonary fungal infection. Surprisingly, systemic vaccination induced a population of tetramer(+) CD4(+) T cells enriched within the pulmonary vasculature, and expressing CXCR3 and CX3CR1, that migrated to the lung tissue upon challenge and efficiently protected mice against infection. Mucosal vaccine priming of Trm may not reliably protect against mucosal pathogens. 2020-01-03 2020-05 /pmc/articles/PMC7183437/ /pubmed/31900406 http://dx.doi.org/10.1038/s41385-019-0244-3 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Dobson, Hannah E. Dias, Lucas Dos Santos Kohn, Elaine M. Fites, Scott Wiesner, Darin L. Dileepan, Thamotharampillai Kujoth, Gregory C. Abraham, Ambily Ostroff, Gary R. Klein, Bruce S. Wüthrich, Marcel Antigen discovery unveils resident memory and migratory cell roles in antifungal resistance |
title | Antigen discovery unveils resident memory and migratory cell roles in antifungal resistance |
title_full | Antigen discovery unveils resident memory and migratory cell roles in antifungal resistance |
title_fullStr | Antigen discovery unveils resident memory and migratory cell roles in antifungal resistance |
title_full_unstemmed | Antigen discovery unveils resident memory and migratory cell roles in antifungal resistance |
title_short | Antigen discovery unveils resident memory and migratory cell roles in antifungal resistance |
title_sort | antigen discovery unveils resident memory and migratory cell roles in antifungal resistance |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7183437/ https://www.ncbi.nlm.nih.gov/pubmed/31900406 http://dx.doi.org/10.1038/s41385-019-0244-3 |
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