Human IRF1 governs macrophagic IFN-γ immunity to mycobacteria

Human IRF1 governs macrophagic IFN-γ immunity to mycobacteria

<p>Inborn errors of human IFN-γ-dependent macrophagic immunity underlie mycobacterial diseases, whereas inborn errors of IFN-α/β-dependent intrinsic immunity underlie viral diseases. Both types of IFNs induce the transcription factor IRF1. We describe unrelated children with inherited complete...

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Main Author: Jérémie Rosain (5900399) (author)
Other Authors: Anna-Lena Neehus (9320912) (author), Jérémy Manry (2160430) (author), Rui Yang (293531) (author), Jérémie Le Pen (18551533) (author), Wassim Daher (240384) (author), Zhiyong Liu (160339) (author), Yi-Hao Chan (7422329) (author), Natalia Tahuil (19483495) (author), Özden Türel (19483498) (author), Mathieu Bourgey (73692) (author), Masato Ogishi (699705) (author), Jean-Marc Doisne (19483501) (author), Helena M. Izquierdo (19483504) (author), Takayoshi Shirasaki (10098660) (author), Tom Le Voyer (18551572) (author), Antoine Guérin (18519939) (author), Paul Bastard (12967485) (author), Marcela Moncada-Vélez (19483408) (author), Ji Eun Han (18519936) (author), Taushif Khan (691254) (author), Franck Rapaport (243876) (author), Seon-Hui Hong (15016838) (author), Andrew Cheung (6485498) (author), Kathrin Haake (15171424) (author), Barbara C. Mindt (11711510) (author), Laura Pérez (234237) (author), Quentin Philippot (558140) (author), Danyel Lee (19483507) (author), Peng Zhang (2071) (author), Darawan Rinchai (742366) (author), Fatima Al Ali (13210926) (author), Manar Mahmoud Ahmad Ata (19483510) (author), Mahbuba Rahman (198499) (author), Jessica N. Peel (19342513) (author), Søren Heissel (5566529) (author), Henrik Molina (1264617) (author), Yasemin Kendir-Demirkol (19342510) (author), Rasheed Bailey (19483513) (author), Shuxiang Zhao (17335719) (author), Jonathan Bohlen (5368448) (author), Mathieu Mancini (11677705) (author), Yoann Seeleuthner (10232517) (author), Marie Roelens (14038091) (author), Lazaro Lorenzo (5155025) (author), Camille Soudée (19342519) (author), María Elvira Josefina Paz (19483516) (author), María Laura González (6238796) (author), Mohamed Jeljeli (5636693) (author), Jean Soulier (15105097) (author), Serge Romana (4260157) (author), Anne-Sophie L’Honneur (5451995) (author), Marie Materna (18387156) (author), Rubén Martínez-Barricarte (19483519) (author), Mathieu Pochon (19483522) (author), Carmen Oleaga-Quintas (19483525) (author), Alexandre Michev (19342507) (author), Mélanie Migaud (5913107) (author), Romain Lévy (18551752) (author), Marie-Alexandra Alyanakian (9518273) (author), Flore Rozenberg (243050) (author), Carys A. Croft (6310997) (author), Guillaume Vogt (64695) (author), Jean-François Emile (64705) (author), Laurent Kremer (37664) (author), Cindy S. Ma (19000769) (author), Jörg H. Fritz (11528196) (author), Stanley M. Lemon (10017699) (author), András N. Spaan (18519927) (author), Nicolas Manel (271967) (author), Laurent Abel (69833) (author), Margaret R. MacDonald (9444081) (author), Stéphanie Boisson-Dupuis (64693) (author), Nico Marr (349853) (author), Stuart G. Tangye (18519960) (author), James P. Di Santo (19483528) (author), Qian Zhang (49333) (author), Shen-Ying Zhang (140174) (author), Charles M. Rice (9110743) (author), Vivien Béziat (204259) (author), Nico Lachmann (3507401) (author), David Langlais (216222) (author), Jean-Laurent Casanova (64712) (author), Philippe Gros (91626) (author), Jacinta Bustamante (64702) (author)
Published: 2023
Subjects:
Biological sciences
Genetics
Microbiology
Biomedical and clinical sciences
Immunology
inborn errors of immunity
Mycobacterium
interferon-γ
interferon-stimulated geneI
RF1
viruses
macrophages
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Summary:<p>Inborn errors of human IFN-γ-dependent macrophagic immunity underlie mycobacterial diseases, whereas inborn errors of IFN-α/β-dependent intrinsic immunity underlie viral diseases. Both types of IFNs induce the transcription factor IRF1. We describe unrelated children with inherited complete IRF1 deficiency and early-onset, multiple, life-threatening diseases caused by weakly virulent mycobacteria and related intramacrophagic pathogens. These children have no history of severe viral disease, despite exposure to many viruses, including SARS-CoV-2, which is life-threatening in individuals with impaired IFN-α/β immunity. In leukocytes or fibroblasts stimulated in vitro, IRF1-dependent responses to IFN-γ are, both quantitatively and qualitatively, much stronger than those to IFN-α/β. Moreover, IRF1-deficient mononuclear phagocytes do not control mycobacteria and related pathogens normally when stimulated with IFN-γ. By contrast, IFN-α/β-dependent intrinsic immunity to nine viruses, including SARS-CoV-2, is almost normal in IRF1-deficient fibroblasts. Human IRF1 is essential for IFN-γ-dependent macrophagic immunity to mycobacteria, but largely redundant for IFN-α/β-dependent antiviral immunity.</p><h2>Other Information</h2> <p> Published in: Cell<br> License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1016/j.cell.2022.12.038" target="_blank">https://dx.doi.org/10.1016/j.cell.2022.12.038</a></p>

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