Life-threatening influenza and impaired interferon amplification in human IRF7 deficiency

Michael J. Ciancanelli, Sarah X L Huang, Priya Luthra, Hannah Garner, Yuval Itan, Stefano Volpi, Fabien G. Lafaille, Céline Trouillet, Mirco Schmolke, Randy A. Albrecht, Elisabeth Israelsson, Hye Kyung Lim, Melina Casadio, Tamar Hermesh, Lazaro Lorenzo, Lawrence W. Leung, Vincent Pedergnana, Bertrand Boisson, Satoshi Okada, Capucine Picard & 12 others Benedicte Ringuier, Françoise Troussier, Damien J. Chaussabel, Laurent Abel, Isabelle Pellier, Luigi D. Notarangelo, Adolfo García-Sastre, Christopher F. Basler, Frédéric Geissmann, Shen Ying Zhang, Hans Willem Snoeck, Jean Laurent Casanova

Research output: Contribution to journalArticle

122 Citations (Scopus)

Abstract

Severe influenza disease strikes otherwise healthy children and remains unexplained.We report compound heterozygous null mutations in IRF7, which encodes the transcription factor interferon regulatory factor 7, in an otherwise healthy child who suffered life-threatening influenza during primary infection. In response to influenza virus, the patient's leukocytes and plasmacytoid dendritic cells produced very little type I and III interferons (IFNs). Moreover, the patient's dermal fibroblasts and induced pluripotent stem cell (iPSC)-derived pulmonary epithelial cells produced reduced amounts of type I IFN and displayed increased influenza virus replication.These findings suggest that IRF7-dependent amplification of type I and III IFNs is required for protection against primary infection by influenza virus in humans. They also show that severe influenza may result from single-gene inborn errors of immunity.

Original languageEnglish
Pages (from-to)448-453
Number of pages6
JournalScience
Volume348
Issue number6233
DOIs
Publication statusPublished - 24 Apr 2015
Externally publishedYes

Fingerprint

Interferon Type I
Interferons
Human Influenza
Orthomyxoviridae
Interferon Regulatory Factor-7
Induced Pluripotent Stem Cells
Virus Replication
Infection
Dendritic Cells
Immunity
Leukocytes
Transcription Factors
Epithelial Cells
Lung
Skin
Mutation
Genes

ASJC Scopus subject areas

  • Medicine(all)
  • General

Cite this

Ciancanelli, M. J., Huang, S. X. L., Luthra, P., Garner, H., Itan, Y., Volpi, S., ... Casanova, J. L. (2015). Life-threatening influenza and impaired interferon amplification in human IRF7 deficiency. Science, 348(6233), 448-453. https://doi.org/10.1126/science.aaa1578

Life-threatening influenza and impaired interferon amplification in human IRF7 deficiency. / Ciancanelli, Michael J.; Huang, Sarah X L; Luthra, Priya; Garner, Hannah; Itan, Yuval; Volpi, Stefano; Lafaille, Fabien G.; Trouillet, Céline; Schmolke, Mirco; Albrecht, Randy A.; Israelsson, Elisabeth; Lim, Hye Kyung; Casadio, Melina; Hermesh, Tamar; Lorenzo, Lazaro; Leung, Lawrence W.; Pedergnana, Vincent; Boisson, Bertrand; Okada, Satoshi; Picard, Capucine; Ringuier, Benedicte; Troussier, Françoise; Chaussabel, Damien J.; Abel, Laurent; Pellier, Isabelle; Notarangelo, Luigi D.; García-Sastre, Adolfo; Basler, Christopher F.; Geissmann, Frédéric; Zhang, Shen Ying; Snoeck, Hans Willem; Casanova, Jean Laurent.

In: Science, Vol. 348, No. 6233, 24.04.2015, p. 448-453.

Research output: Contribution to journalArticle

Ciancanelli, MJ, Huang, SXL, Luthra, P, Garner, H, Itan, Y, Volpi, S, Lafaille, FG, Trouillet, C, Schmolke, M, Albrecht, RA, Israelsson, E, Lim, HK, Casadio, M, Hermesh, T, Lorenzo, L, Leung, LW, Pedergnana, V, Boisson, B, Okada, S, Picard, C, Ringuier, B, Troussier, F, Chaussabel, DJ, Abel, L, Pellier, I, Notarangelo, LD, García-Sastre, A, Basler, CF, Geissmann, F, Zhang, SY, Snoeck, HW & Casanova, JL 2015, 'Life-threatening influenza and impaired interferon amplification in human IRF7 deficiency', Science, vol. 348, no. 6233, pp. 448-453. https://doi.org/10.1126/science.aaa1578
Ciancanelli MJ, Huang SXL, Luthra P, Garner H, Itan Y, Volpi S et al. Life-threatening influenza and impaired interferon amplification in human IRF7 deficiency. Science. 2015 Apr 24;348(6233):448-453. https://doi.org/10.1126/science.aaa1578
Ciancanelli, Michael J. ; Huang, Sarah X L ; Luthra, Priya ; Garner, Hannah ; Itan, Yuval ; Volpi, Stefano ; Lafaille, Fabien G. ; Trouillet, Céline ; Schmolke, Mirco ; Albrecht, Randy A. ; Israelsson, Elisabeth ; Lim, Hye Kyung ; Casadio, Melina ; Hermesh, Tamar ; Lorenzo, Lazaro ; Leung, Lawrence W. ; Pedergnana, Vincent ; Boisson, Bertrand ; Okada, Satoshi ; Picard, Capucine ; Ringuier, Benedicte ; Troussier, Françoise ; Chaussabel, Damien J. ; Abel, Laurent ; Pellier, Isabelle ; Notarangelo, Luigi D. ; García-Sastre, Adolfo ; Basler, Christopher F. ; Geissmann, Frédéric ; Zhang, Shen Ying ; Snoeck, Hans Willem ; Casanova, Jean Laurent. / Life-threatening influenza and impaired interferon amplification in human IRF7 deficiency. In: Science. 2015 ; Vol. 348, No. 6233. pp. 448-453.
@article{e24713e1b84642f09872c694d1013590,
title = "Life-threatening influenza and impaired interferon amplification in human IRF7 deficiency",
abstract = "Severe influenza disease strikes otherwise healthy children and remains unexplained.We report compound heterozygous null mutations in IRF7, which encodes the transcription factor interferon regulatory factor 7, in an otherwise healthy child who suffered life-threatening influenza during primary infection. In response to influenza virus, the patient's leukocytes and plasmacytoid dendritic cells produced very little type I and III interferons (IFNs). Moreover, the patient's dermal fibroblasts and induced pluripotent stem cell (iPSC)-derived pulmonary epithelial cells produced reduced amounts of type I IFN and displayed increased influenza virus replication.These findings suggest that IRF7-dependent amplification of type I and III IFNs is required for protection against primary infection by influenza virus in humans. They also show that severe influenza may result from single-gene inborn errors of immunity.",
author = "Ciancanelli, {Michael J.} and Huang, {Sarah X L} and Priya Luthra and Hannah Garner and Yuval Itan and Stefano Volpi and Lafaille, {Fabien G.} and C{\'e}line Trouillet and Mirco Schmolke and Albrecht, {Randy A.} and Elisabeth Israelsson and Lim, {Hye Kyung} and Melina Casadio and Tamar Hermesh and Lazaro Lorenzo and Leung, {Lawrence W.} and Vincent Pedergnana and Bertrand Boisson and Satoshi Okada and Capucine Picard and Benedicte Ringuier and Fran{\cc}oise Troussier and Chaussabel, {Damien J.} and Laurent Abel and Isabelle Pellier and Notarangelo, {Luigi D.} and Adolfo Garc{\'i}a-Sastre and Basler, {Christopher F.} and Fr{\'e}d{\'e}ric Geissmann and Zhang, {Shen Ying} and Snoeck, {Hans Willem} and Casanova, {Jean Laurent}",
year = "2015",
month = "4",
day = "24",
doi = "10.1126/science.aaa1578",
language = "English",
volume = "348",
pages = "448--453",
journal = "Science",
issn = "0036-8075",
publisher = "American Association for the Advancement of Science",
number = "6233",

}

TY - JOUR

T1 - Life-threatening influenza and impaired interferon amplification in human IRF7 deficiency

AU - Ciancanelli, Michael J.

AU - Huang, Sarah X L

AU - Luthra, Priya

AU - Garner, Hannah

AU - Itan, Yuval

AU - Volpi, Stefano

AU - Lafaille, Fabien G.

AU - Trouillet, Céline

AU - Schmolke, Mirco

AU - Albrecht, Randy A.

AU - Israelsson, Elisabeth

AU - Lim, Hye Kyung

AU - Casadio, Melina

AU - Hermesh, Tamar

AU - Lorenzo, Lazaro

AU - Leung, Lawrence W.

AU - Pedergnana, Vincent

AU - Boisson, Bertrand

AU - Okada, Satoshi

AU - Picard, Capucine

AU - Ringuier, Benedicte

AU - Troussier, Françoise

AU - Chaussabel, Damien J.

AU - Abel, Laurent

AU - Pellier, Isabelle

AU - Notarangelo, Luigi D.

AU - García-Sastre, Adolfo

AU - Basler, Christopher F.

AU - Geissmann, Frédéric

AU - Zhang, Shen Ying

AU - Snoeck, Hans Willem

AU - Casanova, Jean Laurent

PY - 2015/4/24

Y1 - 2015/4/24

N2 - Severe influenza disease strikes otherwise healthy children and remains unexplained.We report compound heterozygous null mutations in IRF7, which encodes the transcription factor interferon regulatory factor 7, in an otherwise healthy child who suffered life-threatening influenza during primary infection. In response to influenza virus, the patient's leukocytes and plasmacytoid dendritic cells produced very little type I and III interferons (IFNs). Moreover, the patient's dermal fibroblasts and induced pluripotent stem cell (iPSC)-derived pulmonary epithelial cells produced reduced amounts of type I IFN and displayed increased influenza virus replication.These findings suggest that IRF7-dependent amplification of type I and III IFNs is required for protection against primary infection by influenza virus in humans. They also show that severe influenza may result from single-gene inborn errors of immunity.

AB - Severe influenza disease strikes otherwise healthy children and remains unexplained.We report compound heterozygous null mutations in IRF7, which encodes the transcription factor interferon regulatory factor 7, in an otherwise healthy child who suffered life-threatening influenza during primary infection. In response to influenza virus, the patient's leukocytes and plasmacytoid dendritic cells produced very little type I and III interferons (IFNs). Moreover, the patient's dermal fibroblasts and induced pluripotent stem cell (iPSC)-derived pulmonary epithelial cells produced reduced amounts of type I IFN and displayed increased influenza virus replication.These findings suggest that IRF7-dependent amplification of type I and III IFNs is required for protection against primary infection by influenza virus in humans. They also show that severe influenza may result from single-gene inborn errors of immunity.

UR - http://www.scopus.com/inward/record.url?scp=84928377935&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84928377935&partnerID=8YFLogxK

U2 - 10.1126/science.aaa1578

DO - 10.1126/science.aaa1578

M3 - Article

VL - 348

SP - 448

EP - 453

JO - Science

JF - Science

SN - 0036-8075

IS - 6233

ER -