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Type I IFN ineffectively activates neonatal dendritic cells limiting respiratory antiviral T cell responses
Insufficient T cell responses contribute to the increased burden of viral respiratory disease in infancy. Neonatal dendritic cells (DCs) often provide defective activation of pathogen-specific T cells through mechanisms that are incompletely understood, which hinders vaccine design for this vulnerab...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7044048/ https://www.ncbi.nlm.nih.gov/pubmed/31797910 http://dx.doi.org/10.1038/s41385-019-0234-5 |
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author | Lau-Kilby, Annie W. Turfkruyer, Mathilde Kehl, Margaret Yang, Lijuan Buchholz, Ursula J. Hickey, Kimberly Malloy, Allison M.W. |
author_facet | Lau-Kilby, Annie W. Turfkruyer, Mathilde Kehl, Margaret Yang, Lijuan Buchholz, Ursula J. Hickey, Kimberly Malloy, Allison M.W. |
author_sort | Lau-Kilby, Annie W. |
collection | PubMed |
description | Insufficient T cell responses contribute to the increased burden of viral respiratory disease in infancy. Neonatal dendritic cells (DCs) often provide defective activation of pathogen-specific T cells through mechanisms that are incompletely understood, which hinders vaccine design for this vulnerable age group. Enhancing our characterization of neonatal DC sub-specialization and function is therefore critical to developing their potential for immunomodulation of T cell responses. In this study, we engineered respiratory syncytial virus (RSV) to express a model protein, ovalbumin, to track antigen-presenting DCs in vivo. We found that murine neonatal conventional DC1s (cDC1s) efficiently migrated and presented RSV-derived antigen, challenging the paradigm that neonatal DCs are globally immature. In a key observation, however, we discovered that during infection neonatal cDC1s presenting viral antigen were unable to upregulate costimulatory molecules in response to type I interferons (IFN-I), contributing to poor antiviral T cell responses. Importantly, we showed that the deficient response to IFN-I was also exhibited by human neonatal cDC1s, independent of infection. These findings reveal a functionally distinct response to IFN-I by neonatal cDC1s that may leave young infants susceptible to viral infections, and provide a new target for exploration, in light of failed efforts to design neonatal RSV vaccines. |
format | Online Article Text |
id | pubmed-7044048 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
record_format | MEDLINE/PubMed |
spelling | pubmed-70440482020-06-04 Type I IFN ineffectively activates neonatal dendritic cells limiting respiratory antiviral T cell responses Lau-Kilby, Annie W. Turfkruyer, Mathilde Kehl, Margaret Yang, Lijuan Buchholz, Ursula J. Hickey, Kimberly Malloy, Allison M.W. Mucosal Immunol Article Insufficient T cell responses contribute to the increased burden of viral respiratory disease in infancy. Neonatal dendritic cells (DCs) often provide defective activation of pathogen-specific T cells through mechanisms that are incompletely understood, which hinders vaccine design for this vulnerable age group. Enhancing our characterization of neonatal DC sub-specialization and function is therefore critical to developing their potential for immunomodulation of T cell responses. In this study, we engineered respiratory syncytial virus (RSV) to express a model protein, ovalbumin, to track antigen-presenting DCs in vivo. We found that murine neonatal conventional DC1s (cDC1s) efficiently migrated and presented RSV-derived antigen, challenging the paradigm that neonatal DCs are globally immature. In a key observation, however, we discovered that during infection neonatal cDC1s presenting viral antigen were unable to upregulate costimulatory molecules in response to type I interferons (IFN-I), contributing to poor antiviral T cell responses. Importantly, we showed that the deficient response to IFN-I was also exhibited by human neonatal cDC1s, independent of infection. These findings reveal a functionally distinct response to IFN-I by neonatal cDC1s that may leave young infants susceptible to viral infections, and provide a new target for exploration, in light of failed efforts to design neonatal RSV vaccines. 2019-12-04 2020-03 /pmc/articles/PMC7044048/ /pubmed/31797910 http://dx.doi.org/10.1038/s41385-019-0234-5 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 Lau-Kilby, Annie W. Turfkruyer, Mathilde Kehl, Margaret Yang, Lijuan Buchholz, Ursula J. Hickey, Kimberly Malloy, Allison M.W. Type I IFN ineffectively activates neonatal dendritic cells limiting respiratory antiviral T cell responses |
title | Type I IFN ineffectively activates neonatal dendritic cells limiting respiratory antiviral T cell responses |
title_full | Type I IFN ineffectively activates neonatal dendritic cells limiting respiratory antiviral T cell responses |
title_fullStr | Type I IFN ineffectively activates neonatal dendritic cells limiting respiratory antiviral T cell responses |
title_full_unstemmed | Type I IFN ineffectively activates neonatal dendritic cells limiting respiratory antiviral T cell responses |
title_short | Type I IFN ineffectively activates neonatal dendritic cells limiting respiratory antiviral T cell responses |
title_sort | type i ifn ineffectively activates neonatal dendritic cells limiting respiratory antiviral t cell responses |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7044048/ https://www.ncbi.nlm.nih.gov/pubmed/31797910 http://dx.doi.org/10.1038/s41385-019-0234-5 |
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