Critical Role of Plasmacytoid Dendritic Cells in Regulating Gene Expression and Innate Immune Responses to Human Rhinovirus-16
Though human rhinoviruses (HRVs) are usually innocuous viruses, they can trigger serious consequences in certain individuals, especially in the setting of impaired interferon (IFN) synthesis. Plasmacytoid dendritic cells (pDCs) are key IFN producing cells, though we know little about the role of pDC...
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doaj-e3d2b3f2b66340a693c53448ec1787ed2020-11-24T21:14:36ZengFrontiers Media S.A.Frontiers in Immunology1664-32242017-10-01810.3389/fimmu.2017.01351301208Critical Role of Plasmacytoid Dendritic Cells in Regulating Gene Expression and Innate Immune Responses to Human Rhinovirus-16Yang Xi0Niamh M. Troy1Denise Anderson2Olga M. Pena3Jason P. Lynch4Simon Phipps5Anthony Bosco6John W. Upham7John W. Upham8Lung and Allergy Research Center, Diamantina Institute, The University of Queensland, Brisbane, QLD, AustraliaSystems Immunology, Telethon Kids Institute, The University of Western Australia, Perth, WA, AustraliaSystems Immunology, Telethon Kids Institute, The University of Western Australia, Perth, WA, AustraliaLung and Allergy Research Center, Diamantina Institute, The University of Queensland, Brisbane, QLD, AustraliaRespiratory Immunology Group, QIMR Berghofer Medical Research Institute, Herston, QLD, AustraliaRespiratory Immunology Group, QIMR Berghofer Medical Research Institute, Herston, QLD, AustraliaSystems Immunology, Telethon Kids Institute, The University of Western Australia, Perth, WA, AustraliaLung and Allergy Research Center, Diamantina Institute, The University of Queensland, Brisbane, QLD, AustraliaDepartment of Respiratory Medicine, Princess Alexandra Hospital, Woolloongabba, QLD, AustraliaThough human rhinoviruses (HRVs) are usually innocuous viruses, they can trigger serious consequences in certain individuals, especially in the setting of impaired interferon (IFN) synthesis. Plasmacytoid dendritic cells (pDCs) are key IFN producing cells, though we know little about the role of pDC in HRV-induced immune responses. Herein, we used gene expression microarrays to examine HRV-activated peripheral blood mononuclear cells (PBMCs) from healthy people, in combination with pDC depletion, to assess whether observed gene expression patterns were pDC dependent. As expected, pDC depletion led to a major reduction in IFN-α release. This was associated with profound differences in gene expression between intact PBMC and pDC-depleted PBMC, and major changes in upstream regulators: 70–80% of the HRV activated genes appeared to be pDC dependent. Real-time PCR confirmed key changes in gene expression, in which the following selected genes were shown to be highly pDC dependent: the transcription factor IRF7, both IL-27 chains (IL-27p28 and EBI3), the alpha chain of the IL-15 receptor (IL-15RA) and the IFN-related gene IFI27. HRV-induced IL-6, IFN-γ, and IL-27 protein synthesis were also highly pDC dependent. Supplementing pDC-depleted cultures with recombinant IL-15, IFN-γ, IL-27, or IL-6 was able to restore the IFN-α response, thereby compensating for the absence of pDC. Though pDC comprise only a minority population of migratory leukocytes, our findings highlight the profound extent to which these cells contribute to the immune response to HRV.http://journal.frontiersin.org/article/10.3389/fimmu.2017.01351/fullplasmacytoid dendritic cellshuman rhinovirushuman rhinovirus responsive genesplasmacytoid dendritic cell-dependent gene expressioninnate immune response |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yang Xi Niamh M. Troy Denise Anderson Olga M. Pena Jason P. Lynch Simon Phipps Anthony Bosco John W. Upham John W. Upham |
spellingShingle |
Yang Xi Niamh M. Troy Denise Anderson Olga M. Pena Jason P. Lynch Simon Phipps Anthony Bosco John W. Upham John W. Upham Critical Role of Plasmacytoid Dendritic Cells in Regulating Gene Expression and Innate Immune Responses to Human Rhinovirus-16 Frontiers in Immunology plasmacytoid dendritic cells human rhinovirus human rhinovirus responsive genes plasmacytoid dendritic cell-dependent gene expression innate immune response |
author_facet |
Yang Xi Niamh M. Troy Denise Anderson Olga M. Pena Jason P. Lynch Simon Phipps Anthony Bosco John W. Upham John W. Upham |
author_sort |
Yang Xi |
title |
Critical Role of Plasmacytoid Dendritic Cells in Regulating Gene Expression and Innate Immune Responses to Human Rhinovirus-16 |
title_short |
Critical Role of Plasmacytoid Dendritic Cells in Regulating Gene Expression and Innate Immune Responses to Human Rhinovirus-16 |
title_full |
Critical Role of Plasmacytoid Dendritic Cells in Regulating Gene Expression and Innate Immune Responses to Human Rhinovirus-16 |
title_fullStr |
Critical Role of Plasmacytoid Dendritic Cells in Regulating Gene Expression and Innate Immune Responses to Human Rhinovirus-16 |
title_full_unstemmed |
Critical Role of Plasmacytoid Dendritic Cells in Regulating Gene Expression and Innate Immune Responses to Human Rhinovirus-16 |
title_sort |
critical role of plasmacytoid dendritic cells in regulating gene expression and innate immune responses to human rhinovirus-16 |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2017-10-01 |
description |
Though human rhinoviruses (HRVs) are usually innocuous viruses, they can trigger serious consequences in certain individuals, especially in the setting of impaired interferon (IFN) synthesis. Plasmacytoid dendritic cells (pDCs) are key IFN producing cells, though we know little about the role of pDC in HRV-induced immune responses. Herein, we used gene expression microarrays to examine HRV-activated peripheral blood mononuclear cells (PBMCs) from healthy people, in combination with pDC depletion, to assess whether observed gene expression patterns were pDC dependent. As expected, pDC depletion led to a major reduction in IFN-α release. This was associated with profound differences in gene expression between intact PBMC and pDC-depleted PBMC, and major changes in upstream regulators: 70–80% of the HRV activated genes appeared to be pDC dependent. Real-time PCR confirmed key changes in gene expression, in which the following selected genes were shown to be highly pDC dependent: the transcription factor IRF7, both IL-27 chains (IL-27p28 and EBI3), the alpha chain of the IL-15 receptor (IL-15RA) and the IFN-related gene IFI27. HRV-induced IL-6, IFN-γ, and IL-27 protein synthesis were also highly pDC dependent. Supplementing pDC-depleted cultures with recombinant IL-15, IFN-γ, IL-27, or IL-6 was able to restore the IFN-α response, thereby compensating for the absence of pDC. Though pDC comprise only a minority population of migratory leukocytes, our findings highlight the profound extent to which these cells contribute to the immune response to HRV. |
topic |
plasmacytoid dendritic cells human rhinovirus human rhinovirus responsive genes plasmacytoid dendritic cell-dependent gene expression innate immune response |
url |
http://journal.frontiersin.org/article/10.3389/fimmu.2017.01351/full |
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