| Literature DB >> 25814066 |
Michael J Ciancanelli1, Sarah X L Huang2, Priya Luthra3, Hannah Garner4, Yuval Itan1, Stefano Volpi5, Fabien G Lafaille1, Céline Trouillet4, Mirco Schmolke3, Randy A Albrecht6, Elisabeth Israelsson7, Hye Kyung Lim1, Melina Casadio1, Tamar Hermesh1, Lazaro Lorenzo8, Lawrence W Leung3, Vincent Pedergnana8, Bertrand Boisson1, Satoshi Okada9, Capucine Picard10, Benedicte Ringuier11, Françoise Troussier12, Damien Chaussabel13, Laurent Abel14, Isabelle Pellier15, Luigi D Notarangelo16, Adolfo García-Sastre17, Christopher F Basler3, Frédéric Geissmann4, Shen-Ying Zhang14, Hans-Willem Snoeck2, Jean-Laurent Casanova18.
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.Entities:
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Year: 2015 PMID： 25814066 PMCID： PMC4431581 DOI： 10.1126/science.aaa1578
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 47.728