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Impaired gamma delta T cell-derived IL-17A and inflammasome activation during early respiratory syncytial virus infection in infants
Respiratory syncytial virus (RSV) infection remains a significant global health burden disproportionately affecting infants and leading to long-term lung disease. IL-17A has been shown to be involved in regulating viral and allergic lung inflammatory responses, which has led to a more recent interes...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4323740/ https://www.ncbi.nlm.nih.gov/pubmed/25267484 http://dx.doi.org/10.1038/icb.2014.79 |
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author | Huang, Huaqiong Saravia, Jordy You, Dahui Shaw, Aaron J. Cormier, Stephania A. |
author_facet | Huang, Huaqiong Saravia, Jordy You, Dahui Shaw, Aaron J. Cormier, Stephania A. |
author_sort | Huang, Huaqiong |
collection | PubMed |
description | Respiratory syncytial virus (RSV) infection remains a significant global health burden disproportionately affecting infants and leading to long-term lung disease. IL-17A has been shown to be involved in regulating viral and allergic lung inflammatory responses, which has led to a more recent interest in its role in RSV infection. Using a neonatal mouse model of RSV, we demonstrate that neonates fail to develop IL-17A responses compared to adult mice; the main immediate IL-17A contributor in adults were γδ T cells. Antibody neutralization of IL-17A in adult mice caused increased lung inflammation and airway mucus from RSV, while exogenous IL-17A administration to RSV-infected neonates caused decreased inflammation but no change in airway mucus. We also observed a lack of pro-inflammatory cytokine production (IL-1β, IL-6) from infected neonates. Using human cord blood mononuclear cells (CBMCs) and adult peripheral blood mononuclear cells (PBMCs), we compared inflammasome activation by direct retinoic acid-inducible gene I (RIG-I) agonism; CBMCs failed to induce pro-inflammatory cytokines or IL-17A(+) γδ T cells compared to PBMCs. Our results indicate that RSV disease severity is in part mediated by a lack of inflammasome activation and IL-17A production in neonates. |
format | Online Article Text |
id | pubmed-4323740 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
record_format | MEDLINE/PubMed |
spelling | pubmed-43237402015-08-01 Impaired gamma delta T cell-derived IL-17A and inflammasome activation during early respiratory syncytial virus infection in infants Huang, Huaqiong Saravia, Jordy You, Dahui Shaw, Aaron J. Cormier, Stephania A. Immunol Cell Biol Article Respiratory syncytial virus (RSV) infection remains a significant global health burden disproportionately affecting infants and leading to long-term lung disease. IL-17A has been shown to be involved in regulating viral and allergic lung inflammatory responses, which has led to a more recent interest in its role in RSV infection. Using a neonatal mouse model of RSV, we demonstrate that neonates fail to develop IL-17A responses compared to adult mice; the main immediate IL-17A contributor in adults were γδ T cells. Antibody neutralization of IL-17A in adult mice caused increased lung inflammation and airway mucus from RSV, while exogenous IL-17A administration to RSV-infected neonates caused decreased inflammation but no change in airway mucus. We also observed a lack of pro-inflammatory cytokine production (IL-1β, IL-6) from infected neonates. Using human cord blood mononuclear cells (CBMCs) and adult peripheral blood mononuclear cells (PBMCs), we compared inflammasome activation by direct retinoic acid-inducible gene I (RIG-I) agonism; CBMCs failed to induce pro-inflammatory cytokines or IL-17A(+) γδ T cells compared to PBMCs. Our results indicate that RSV disease severity is in part mediated by a lack of inflammasome activation and IL-17A production in neonates. 2014-09-30 2015-02 /pmc/articles/PMC4323740/ /pubmed/25267484 http://dx.doi.org/10.1038/icb.2014.79 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 Huang, Huaqiong Saravia, Jordy You, Dahui Shaw, Aaron J. Cormier, Stephania A. Impaired gamma delta T cell-derived IL-17A and inflammasome activation during early respiratory syncytial virus infection in infants |
title | Impaired gamma delta T cell-derived IL-17A and inflammasome activation during early respiratory syncytial virus infection in infants |
title_full | Impaired gamma delta T cell-derived IL-17A and inflammasome activation during early respiratory syncytial virus infection in infants |
title_fullStr | Impaired gamma delta T cell-derived IL-17A and inflammasome activation during early respiratory syncytial virus infection in infants |
title_full_unstemmed | Impaired gamma delta T cell-derived IL-17A and inflammasome activation during early respiratory syncytial virus infection in infants |
title_short | Impaired gamma delta T cell-derived IL-17A and inflammasome activation during early respiratory syncytial virus infection in infants |
title_sort | impaired gamma delta t cell-derived il-17a and inflammasome activation during early respiratory syncytial virus infection in infants |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4323740/ https://www.ncbi.nlm.nih.gov/pubmed/25267484 http://dx.doi.org/10.1038/icb.2014.79 |
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