Infectious disease. 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; Benedicte Ringuier; Françoise Troussier; Damien Chaussabel; Laurent Abel; Isabelle Pellier; Luigi D Notarangelo; Adolfo García-Sastre; Christopher F Basler; Frederic Geissmann; Shen-Ying Zhang; Hans-Willem Snoeck; Jean-Laurent Casanova

doi:10.1126/science.aaa1578

Infectious disease. 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 PicardBenedicte Ringuier, Françoise Troussier, Damien Chaussabel, Laurent Abel, Isabelle Pellier, Luigi D Notarangelo, Adolfo García-Sastre, Christopher F Basler, Frederic Geissmann, Shen-Ying Zhang, Hans-Willem Snoeck, Jean-Laurent Casanova

Inflammation Biology

Research output: Contribution to journal › Article › peer-review

370 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 language	English
Pages (from-to)	448-453
Number of pages	6
Journal	Science
Volume	348
Issue number	6233
DOIs	https://doi.org/10.1126/science.aaa1578
Publication status	Published - 24 Apr 2015

Keywords

Child
Dendritic Cells
Female
Fibroblasts
Genes, Recessive
Heterozygote
Humans
Induced Pluripotent Stem Cells
Influenza A Virus, H1N1 Subtype
Influenza, Human
Interferon Regulatory Factor-7
Interferon Type I
Leukocytes
Lung
Mutation
Respiratory Distress Syndrome, Adult
Respiratory Mucosa

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1126/science.aaa1578

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Ciancanelli, M. J., Huang, S. X. L., Luthra, P., Garner, H., Itan, Y., Volpi, S., Lafaille, F. G., Trouillet, C., Schmolke, M., Albrecht, R. A., Israelsson, E., Lim, H. K., Casadio, M., Hermesh, T., Lorenzo, L., Leung, L. W., Pedergnana, V., Boisson, B., Okada, S., ... Casanova, J.-L. (2015). Infectious disease. Life-threatening influenza and impaired interferon amplification in human IRF7 deficiency. Science, 348(6233), 448-453. https://doi.org/10.1126/science.aaa1578

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title = "Infectious disease. 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.",

keywords = "Child, Dendritic Cells, Female, Fibroblasts, Genes, Recessive, Heterozygote, Humans, Induced Pluripotent Stem Cells, Influenza A Virus, H1N1 Subtype, Influenza, Human, Interferon Regulatory Factor-7, Interferon Type I, Leukocytes, Lung, Mutation, Respiratory Distress Syndrome, Adult, Respiratory Mucosa",

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{\c c}oise Troussier and Damien Chaussabel and Laurent Abel and Isabelle Pellier and Notarangelo, {Luigi D} and Adolfo Garc{\'i}a-Sastre and Basler, {Christopher F} and Frederic Geissmann and Shen-Ying Zhang and Hans-Willem Snoeck and Jean-Laurent Casanova",

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doi = "10.1126/science.aaa1578",

language = "English",

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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, D, Abel, L, Pellier, I, Notarangelo, LD, García-Sastre, A, Basler, CF, Geissmann, F, Zhang, S-Y, Snoeck, H-W & Casanova, J-L 2015, 'Infectious disease. 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

TY - JOUR

T1 - Infectious disease. 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

AU - Abel, Laurent

AU - Pellier, Isabelle

AU - Notarangelo, Luigi D

AU - García-Sastre, Adolfo

AU - Basler, Christopher F

AU - Geissmann, Frederic

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.

KW - Child

KW - Dendritic Cells

KW - Female

KW - Fibroblasts

KW - Genes, Recessive

KW - Heterozygote

KW - Humans

KW - Induced Pluripotent Stem Cells

KW - Influenza A Virus, H1N1 Subtype

KW - Influenza, Human

KW - Interferon Regulatory Factor-7

KW - Interferon Type I

KW - Leukocytes

KW - Lung

KW - Mutation

KW - Respiratory Distress Syndrome, Adult

KW - Respiratory Mucosa

U2 - 10.1126/science.aaa1578

DO - 10.1126/science.aaa1578

M3 - Article

C2 - 25814066

SN - 0036-8075

VL - 348

SP - 448

EP - 453

JO - Science

JF - Science

IS - 6233

ER -

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

Abstract

Keywords

UN SDGs

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