Rigid interferon-α subtype responses of human plasmacytoid dendritic cells

Richard Szubin, W. L William Chang, Tamara Greasby, Laurel A Beckett, Nicole Baumgarth

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

The large family of human type I interferon (IFN) includes 13 distinct subtypes of IFN-α, all utilizing a single type I IFN receptor. Many viruses have created evasion strategies to disable this cytokine family, highlighting their importance in antiviral defense. It is unclear what advantage the presence of so many different IFN-α subtypes provides, but functional differences observed among individual IFN-α subtypes suggested that they might play distinct regulatory roles during an immune response. To determine whether IFN-α subtype responses differ depending on a particular type of insult and thus whether IFN-α subtype responses are flexible to adapt to distinct pathogen challenges, we developed a novel nested multiplex reverse transcriptase polymerase chain reaction assay with which we measured expression of all IFN-α subtypes by freshly isolated human plasmacytoid dendritic cells (pDCs), a main source of IFN-α following pathogen challenge. Collectively our data show a remarkable stability in the relative magnitude and the kinetics of induction for each IFN-α subtype produced by pDC. Although various stimuli used, A-, B- and C-class CpGs, live and heat-inactivated influenza viruses and the TLR7 agonist R837 affected the overall magnitude of the response, each IFN-α subtype was induced at statistically similar relative levels and with similar kinetics, thereby revealing a great degree of rigidity in the IFN-α response pattern of pDC. These data are most consistent with the induction of optimized ratios of IFN-α subtypes, each of which may have differing signaling properties or alternatively, a great degree of redundancy in the IFN-α response.

Original languageEnglish (US)
Pages (from-to)749-763
Number of pages15
JournalJournal of Interferon and Cytokine Research
Volume28
Issue number12
DOIs
StatePublished - Dec 2008

Fingerprint

Dendritic Cells
Interferons
imiquimod
Interferon alpha-beta Receptor
Interferon Type I
Multiplex Polymerase Chain Reaction
Orthomyxoviridae
Reverse Transcriptase Polymerase Chain Reaction
Antiviral Agents
Hot Temperature
Cytokines
Viruses

ASJC Scopus subject areas

  • Immunology
  • Virology
  • Cell Biology

Cite this

Rigid interferon-α subtype responses of human plasmacytoid dendritic cells. / Szubin, Richard; Chang, W. L William; Greasby, Tamara; Beckett, Laurel A; Baumgarth, Nicole.

In: Journal of Interferon and Cytokine Research, Vol. 28, No. 12, 12.2008, p. 749-763.

Research output: Contribution to journalArticle

@article{bffb148b5b3442138c1c1e2ee98aa843,
title = "Rigid interferon-α subtype responses of human plasmacytoid dendritic cells",
abstract = "The large family of human type I interferon (IFN) includes 13 distinct subtypes of IFN-α, all utilizing a single type I IFN receptor. Many viruses have created evasion strategies to disable this cytokine family, highlighting their importance in antiviral defense. It is unclear what advantage the presence of so many different IFN-α subtypes provides, but functional differences observed among individual IFN-α subtypes suggested that they might play distinct regulatory roles during an immune response. To determine whether IFN-α subtype responses differ depending on a particular type of insult and thus whether IFN-α subtype responses are flexible to adapt to distinct pathogen challenges, we developed a novel nested multiplex reverse transcriptase polymerase chain reaction assay with which we measured expression of all IFN-α subtypes by freshly isolated human plasmacytoid dendritic cells (pDCs), a main source of IFN-α following pathogen challenge. Collectively our data show a remarkable stability in the relative magnitude and the kinetics of induction for each IFN-α subtype produced by pDC. Although various stimuli used, A-, B- and C-class CpGs, live and heat-inactivated influenza viruses and the TLR7 agonist R837 affected the overall magnitude of the response, each IFN-α subtype was induced at statistically similar relative levels and with similar kinetics, thereby revealing a great degree of rigidity in the IFN-α response pattern of pDC. These data are most consistent with the induction of optimized ratios of IFN-α subtypes, each of which may have differing signaling properties or alternatively, a great degree of redundancy in the IFN-α response.",
author = "Richard Szubin and Chang, {W. L William} and Tamara Greasby and Beckett, {Laurel A} and Nicole Baumgarth",
year = "2008",
month = "12",
doi = "10.1089/jir.2008.0037",
language = "English (US)",
volume = "28",
pages = "749--763",
journal = "Journal of Interferon and Cytokine Research",
issn = "1079-9907",
publisher = "Mary Ann Liebert Inc.",
number = "12",

}

TY - JOUR

T1 - Rigid interferon-α subtype responses of human plasmacytoid dendritic cells

AU - Szubin, Richard

AU - Chang, W. L William

AU - Greasby, Tamara

AU - Beckett, Laurel A

AU - Baumgarth, Nicole

PY - 2008/12

Y1 - 2008/12

N2 - The large family of human type I interferon (IFN) includes 13 distinct subtypes of IFN-α, all utilizing a single type I IFN receptor. Many viruses have created evasion strategies to disable this cytokine family, highlighting their importance in antiviral defense. It is unclear what advantage the presence of so many different IFN-α subtypes provides, but functional differences observed among individual IFN-α subtypes suggested that they might play distinct regulatory roles during an immune response. To determine whether IFN-α subtype responses differ depending on a particular type of insult and thus whether IFN-α subtype responses are flexible to adapt to distinct pathogen challenges, we developed a novel nested multiplex reverse transcriptase polymerase chain reaction assay with which we measured expression of all IFN-α subtypes by freshly isolated human plasmacytoid dendritic cells (pDCs), a main source of IFN-α following pathogen challenge. Collectively our data show a remarkable stability in the relative magnitude and the kinetics of induction for each IFN-α subtype produced by pDC. Although various stimuli used, A-, B- and C-class CpGs, live and heat-inactivated influenza viruses and the TLR7 agonist R837 affected the overall magnitude of the response, each IFN-α subtype was induced at statistically similar relative levels and with similar kinetics, thereby revealing a great degree of rigidity in the IFN-α response pattern of pDC. These data are most consistent with the induction of optimized ratios of IFN-α subtypes, each of which may have differing signaling properties or alternatively, a great degree of redundancy in the IFN-α response.

AB - The large family of human type I interferon (IFN) includes 13 distinct subtypes of IFN-α, all utilizing a single type I IFN receptor. Many viruses have created evasion strategies to disable this cytokine family, highlighting their importance in antiviral defense. It is unclear what advantage the presence of so many different IFN-α subtypes provides, but functional differences observed among individual IFN-α subtypes suggested that they might play distinct regulatory roles during an immune response. To determine whether IFN-α subtype responses differ depending on a particular type of insult and thus whether IFN-α subtype responses are flexible to adapt to distinct pathogen challenges, we developed a novel nested multiplex reverse transcriptase polymerase chain reaction assay with which we measured expression of all IFN-α subtypes by freshly isolated human plasmacytoid dendritic cells (pDCs), a main source of IFN-α following pathogen challenge. Collectively our data show a remarkable stability in the relative magnitude and the kinetics of induction for each IFN-α subtype produced by pDC. Although various stimuli used, A-, B- and C-class CpGs, live and heat-inactivated influenza viruses and the TLR7 agonist R837 affected the overall magnitude of the response, each IFN-α subtype was induced at statistically similar relative levels and with similar kinetics, thereby revealing a great degree of rigidity in the IFN-α response pattern of pDC. These data are most consistent with the induction of optimized ratios of IFN-α subtypes, each of which may have differing signaling properties or alternatively, a great degree of redundancy in the IFN-α response.

UR - http://www.scopus.com/inward/record.url?scp=57149099467&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=57149099467&partnerID=8YFLogxK

U2 - 10.1089/jir.2008.0037

DO - 10.1089/jir.2008.0037

M3 - Article

C2 - 18937549

AN - SCOPUS:57149099467

VL - 28

SP - 749

EP - 763

JO - Journal of Interferon and Cytokine Research

JF - Journal of Interferon and Cytokine Research

SN - 1079-9907

IS - 12

ER -