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

Michael J. Ciancanelli (1) , Sarah X. L. Huang (2) , Priya Luthra (3) , Hannah Garner (4) , Yuval Itan (1) , Stefano Volpi (5, 6) , Fabien G. Lafaille (1) , Céline Trouillet (4) , Mirco Schmolke (3) , Randy A. Albrecht (3) , Elisabeth Israelsson (7) , Hye Kyung Lim (1) , Melina Casadio (1) , Tamar Hermesh (1) , Lazaro Lorenzo (8) , Lawrence W. Leung (3) , Vincent Pedergnana (8) , Bertrand Boisson (1) , Satoshi Okada (1) , Capucine Picard (1, 8) , Benedicte Ringuier (9) , Françoise Troussier (10) , Damien Chaussabel (11, 12) , Laurent Abel (1, 8) , Isabelle Pellier (13, 14) , Luigi D. Notarangelo (5) , Adolfo García-Sastre (3) , Christopher F. Basler (3) , Frédéric Geissmann (4) , Shen-Ying Zhang (3) , Hans-Willem Snoeck (2) , Jean-Laurent Casanova (1, 8, 15)

1 St. Giles Laboratory of Human Genetics of Infectious Diseases
2 CUMC - Columbia University Medical Center
3 MSSM - Icahn School of Medicine at Mount Sinai [New York]
4 CMCBI - Centre for Cellular and Molecular Biology of Inflammation [London, UK]
5 Division of Immunology and The Manton Center for Orphan Disease Research [Boston, MA, USA]
6 UniGe - Università degli studi di Genova = University of Genoa
7 Department of Systems Immunology [Seattle, WA, USA]
8 Imagine - U1163 - Imagine - Institut des maladies génétiques (IHU)
9 Service de chirurgie pédiatrique [CHU Angers]
10 Service de Pédiatrie Générale [CHU Angers]
11 BRI - Benaroya Research Institute [Seattle]
12 Sidra Medical and Research Center [Doha, Qatar]
13 CRCNA - Centre de Recherche en Cancérologie Nantes-Angers
14 Service d'Immunologie Hématologie et Oncologie pédiatriques [CHU Angers]
15 Service d'immuno-hématologie pédiatrique [CHU Necker]

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.

Domaines: Cancer

Michael J. Ciancanelli, Sarah X. L. Huang, Priya Luthra, Hannah Garner, Yuval Itan, et al.. Infectious disease. Life-threatening influenza and impaired interferon amplification in human IRF7 deficiency.. Science, 2015, 348 (6233), pp.448-53. ⟨10.1126/science.aaa1578⟩. ⟨inserm-02517129⟩