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Severe influenza pneumonitis in children with inherited TLR3 deficiency.
Lim, Hye Kyung; Huang, Sarah X L; Chen, Jie; Kerner, Gaspard; Gilliaux, Olivier; Bastard, Paul; Dobbs, Kerry; Hernandez, Nicholas; Goudin, Nicolas; Hasek, Mary L; García Reino, Eduardo Javier; Lafaille, Fabien G; Lorenzo, Lazaro; Luthra, Priya; Kochetkov, Tatiana; Bigio, Benedetta; Boucherit, Soraya; Rozenberg, Flore; Vedrinne, Catherine; Keller, Michael D; Itan, Yuval; García-Sastre, Adolfo; Celard, Marie; Orange, Jordan S; Ciancanelli, Michael J; Meyts, Isabelle; Zhang, Qian; Abel, Laurent; Notarangelo, Luigi D; Snoeck, Hans-Willem; Casanova, Jean-Laurent; Zhang, Shen-Ying.
Afiliación
  • Lim HK; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY.
  • Huang SXL; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale UMR 1163, Paris, France.
  • Chen J; Paris Descartes University, Imagine Institute, Paris, France.
  • Kerner G; Columbia Center for Translational Immunology, Columbia University Medical Center, New York, NY.
  • Gilliaux O; Department of Medicine, Columbia University Medical Center, New York, NY.
  • Bastard P; Center for Stem Cell and Regenerative Medicine, University of Texas Health Science Center at Texas, Houston, TX.
  • Dobbs K; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY.
  • Hernandez N; Department of Infectious Diseases, Shanghai Sixth Hospital, Shanghai Jiaotong University, Shanghai, China.
  • Goudin N; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale UMR 1163, Paris, France.
  • Hasek ML; Paris Descartes University, Imagine Institute, Paris, France.
  • García Reino EJ; Laboratory of Experimental Medicine (ULB222), Medicine Faculty, Libre de Bruxelles University, Brussels, Belgium.
  • Lafaille FG; Department of Pediatrics, University Hospital Center of Charleroi, Charleroi, Belgium.
  • Lorenzo L; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale UMR 1163, Paris, France.
  • Luthra P; Paris Descartes University, Imagine Institute, Paris, France.
  • Kochetkov T; Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.
  • Bigio B; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY.
  • Boucherit S; Cell Imaging Platform Structure Fédérative de Recherche Necker, Institut National de la Santé et de la Recherche Médicale US 24, Paris, France.
  • Rozenberg F; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY.
  • Vedrinne C; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY.
  • Keller MD; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY.
  • Itan Y; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale UMR 1163, Paris, France.
  • García-Sastre A; Paris Descartes University, Imagine Institute, Paris, France.
  • Celard M; Department of Microbiology, Global Health and Emerging Pathogens Institute, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY.
  • Orange JS; Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, NY.
  • Ciancanelli MJ; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY.
  • Meyts I; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY.
  • Zhang Q; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale UMR 1163, Paris, France.
  • Abel L; Paris Descartes University, Imagine Institute, Paris, France.
  • Notarangelo LD; Virology, Cochin-Saint-Vincent de Paul Hospital, Paris Descartes University, Paris, France.
  • Snoeck HW; Department of Anesthesia and Intensive Care Medicine in Cardiovascular Surgery, Louis Pradel Cardiological Hospital, Lyon, France.
  • Casanova JL; Division of Allergy and Immunology, Center for Cancer and Immunology Research, Children's National Health System, Washington, DC.
  • Zhang SY; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY.
J Exp Med ; 216(9): 2038-2056, 2019 09 02.
Article en En | MEDLINE | ID: mdl-31217193
Autosomal recessive IRF7 and IRF9 deficiencies impair type I and III IFN immunity and underlie severe influenza pneumonitis. We report three unrelated children with influenza A virus (IAV) infection manifesting as acute respiratory distress syndrome (IAV-ARDS), heterozygous for rare TLR3 variants (P554S in two patients and P680L in the third) causing autosomal dominant (AD) TLR3 deficiency. AD TLR3 deficiency can underlie herpes simplex virus-1 (HSV-1) encephalitis (HSE) by impairing cortical neuron-intrinsic type I IFN immunity to HSV-1. TLR3-mutated leukocytes produce normal levels of IFNs in response to IAV. In contrast, TLR3-mutated fibroblasts produce lower levels of IFN-ß and -λ, and display enhanced viral susceptibility, upon IAV infection. Moreover, the patients' iPSC-derived pulmonary epithelial cells (PECs) are susceptible to IAV. Treatment with IFN-α2b or IFN-λ1 rescues this phenotype. AD TLR3 deficiency may thus underlie IAV-ARDS by impairing TLR3-dependent, type I and/or III IFN-mediated, PEC-intrinsic immunity. Its clinical penetrance is incomplete for both IAV-ARDS and HSE, consistent with their typically sporadic nature.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Neumonía / Patrón de Herencia / Receptor Toll-Like 3 / Gripe Humana Límite: Child / Child, preschool / Female / Humans / Infant / Male / Newborn Idioma: En Revista: J Exp Med Año: 2019 Tipo del documento: Article
Texto completo
Imprimir
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PubMed Links
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Neumonía / Patrón de Herencia / Receptor Toll-Like 3 / Gripe Humana Límite: Child / Child, preschool / Female / Humans / Infant / Male / Newborn Idioma: En Revista: J Exp Med Año: 2019 Tipo del documento: Article