Critical role of plasmacytoid dendritic cells in regulating gene expression and innate immune responses to human rhinovirus-16

Yang Xi, Niamh M. Troy, Denise Anderson, Olga M. Pena, Jason P. Lynch, Simon Phipps, Anthony Bosco, John W. Upham

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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-a 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.

Original languageEnglish
Article number1351
JournalFrontiers in Immunology
Volume8
Issue numberOCT
DOIs
Publication statusPublished - 25 Oct 2017

Fingerprint

Rhinovirus
Innate Immunity
Dendritic Cells
Interferons
Gene Expression
Interleukin-27
Blood Cells
Interleukin-6
Interleukin-15 Receptors
Genes
Interleukin-15
Real-Time Polymerase Chain Reaction
Leukocytes
Transcription Factors
Viruses
Population

Cite this

Xi, Yang ; Troy, Niamh M. ; Anderson, Denise ; Pena, Olga M. ; Lynch, Jason P. ; Phipps, Simon ; Bosco, Anthony ; Upham, John W. / Critical role of plasmacytoid dendritic cells in regulating gene expression and innate immune responses to human rhinovirus-16. In: Frontiers in Immunology. 2017 ; Vol. 8, No. OCT.
@article{54d2f796a82d4850b05bb9a94de4b16d,
title = "Critical role of plasmacytoid dendritic cells in regulating gene expression and innate immune responses to human rhinovirus-16",
abstract = "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-a 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.",
keywords = "Human rhinovirus, Human rhinovirus responsive genes, Innate immune response, plasmacytoid dendritic cell-dependent gene expression, Plasmacytoid dendritic cells",
author = "Yang Xi and Troy, {Niamh M.} and Denise Anderson and Pena, {Olga M.} and Lynch, {Jason P.} and Simon Phipps and Anthony Bosco and Upham, {John W.}",
year = "2017",
month = "10",
day = "25",
doi = "10.3389/fimmu.2017.01351",
language = "English",
volume = "8",
journal = "Frontiers in Immunology",
issn = "1664-3224",
publisher = "Frontiers Media SA",
number = "OCT",

}

Critical role of plasmacytoid dendritic cells in regulating gene expression and innate immune responses to human rhinovirus-16. / Xi, Yang; Troy, Niamh M.; Anderson, Denise; Pena, Olga M.; Lynch, Jason P.; Phipps, Simon; Bosco, Anthony; Upham, John W.

In: Frontiers in Immunology, Vol. 8, No. OCT, 1351, 25.10.2017.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Critical role of plasmacytoid dendritic cells in regulating gene expression and innate immune responses to human rhinovirus-16

AU - Xi, Yang

AU - Troy, Niamh M.

AU - Anderson, Denise

AU - Pena, Olga M.

AU - Lynch, Jason P.

AU - Phipps, Simon

AU - Bosco, Anthony

AU - Upham, John W.

PY - 2017/10/25

Y1 - 2017/10/25

N2 - 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-a 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.

AB - 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-a 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.

KW - Human rhinovirus

KW - Human rhinovirus responsive genes

KW - Innate immune response

KW - plasmacytoid dendritic cell-dependent gene expression

KW - Plasmacytoid dendritic cells

UR - http://www.scopus.com/inward/record.url?scp=85032171740&partnerID=8YFLogxK

U2 - 10.3389/fimmu.2017.01351

DO - 10.3389/fimmu.2017.01351

M3 - Article

VL - 8

JO - Frontiers in Immunology

JF - Frontiers in Immunology

SN - 1664-3224

IS - OCT

M1 - 1351

ER -