부산대학교 도서관

Keywords inborn errors of immunity; Mycobacterium; interferon-[gamma]; interferon-stimulated gene; IRF1; viruses; macrophages Highlights * Inherited complete human IRF1 deficiency underlies severe mycobacterial disease * Human IRF1 is essential for IFN-[gamma]-dependent macrophagic immunity to mycobacteria * Human IRF1 is essential for IFN-[gamma]- and STAT1-dependent immunity to mycobacteria * Human IRF1 is largely redundant for IFN-[alpha]/[beta]-dependent antiviral intrinsic immunity Summary Inborn errors of human IFN-[gamma]-dependent macrophagic immunity underlie mycobacterial diseases, whereas inborn errors of IFN-[alpha]/[beta]-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-[alpha]/[beta] immunity. In leukocytes or fibroblasts stimulated in vitro, IRF1-dependent responses to IFN-[gamma] are, both quantitatively and qualitatively, much stronger than those to IFN-[alpha]/[beta]. Moreover, IRF1-deficient mononuclear phagocytes do not control mycobacteria and related pathogens normally when stimulated with IFN-[gamma]. By contrast, IFN-[alpha]/[beta]-dependent intrinsic immunity to nine viruses, including SARS-CoV-2, is almost normal in IRF1-deficient fibroblasts. Human IRF1 is essential for IFN-[gamma]-dependent macrophagic immunity to mycobacteria, but largely redundant for IFN-[alpha]/[beta]-dependent antiviral immunity. Author Affiliation: (1) Laboratory of Human Genetics of Infectious Diseases, Inserm U1163, 75015 Paris, France (2) Paris Cité University, Imagine Institute, 75015 Paris, France (3) Institute of Experimental Hematology, REBIRTH Center for Regenerative and Translational Medicine, Hannover Medical School, 30625 Hannover, Germany (4) St. Giles Laboratory of Human Genetics of Infectious Diseases, The Rockefeller University, New York, NY 10065, USA (5) Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY 10065, USA (6) Infectious Disease Research Institute of Montpellier (IRIM), Montpellier University, 34090 Montpellier, France (7) Inserm, IRIM, CNRS, UMR9004, 34090 Montpellier, France (8) Department of Immunology, Del Niño Jesus Hospital, San Miguel de Tucuman, T4000 Tucuman, Argentina (9) Department of Pediatric Infectious Disease, Bezmialem Vakif University Faculty of Medicine, 34093 Istanbul, Turkey (10) Dahdaleh Institute of Genomic Medicine, McGill University, Montreal, QC H3A 0G1, Canada (11) Canadian Centre for Computation Genomics, Montreal, QC H3A 0G1, Canada (12) Innate Immunity Unit, Institut Pasteur, 75015 Paris, France (13) Inserm U1223, 75015 Paris, France (14) Institut Curie, PSL Research University, Inserm U932, 75005 Paris, France (15) Department of Medicine, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7292, USA (16) Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia (17) St. Vincent's Clinical School, Faculty of Medicine, University of NSW, Sydney, NSW 2052, Australia (18) Pediatric Hematology-Immunology and Rheumatology Unit, Necker Hospital for Sick Children, Assistance Publique Hôpitaux de Paris (AP-HP), 75015 Paris, France (19) Department of Immunology, Sidra Medicine, Doha, Qatar (20) Department of Microbiology and Immunology, McGill University, Montreal, QC H3A 0G1, Canada (21) McGill University Research Centre on Complex Traits, McGill University, Montreal, QC H3A 0G1, Canada (22) FOCiS Centre of Excellence in Translational Immunology, McGill University, Montreal, QC H3A 0G1, Canada (23) Department of Immunology and Rheumatology, 'J. P. Garrahan' National Hospital of Pediatrics, C1245 CABA Buenos Aires, Argentina (24) Proteomics Resource Center, The Rockefeller University, New York, NY 10065, USA (25) Umraniye Education and Research Hospital, Department of Pediatric Genetics, 34764 Istanbul, Turkey (26) Study Center for Primary Immunodeficiencies, Necker Hospital for Sick Children, AP-HP, 75015 Paris, France (27) Paris Cité University, 75006 Paris, France (28) Department of Pediatric Pathology, Del Niño Jesus Hospital, San Miguel de Tucuman, T4000 Tucuman, Argentina (29) Central Laboratory, Del Niño Jesus Hospital, San Miguel de Tucuman, T4000 Tucuman, Argentina (30) Cochin University Hospital, Biological Immunology Unit, AP-HP, 75014 Paris, France (31) Inserm/CNRS U944/7212, Paris Cité University, 75006 Paris, France (32) Hematology Laboratory, Saint-Louis Hospital, AP-HP, 75010 Paris, France (33) National Reference Center for Bone Marrow Failures, Saint-Louis and Robert Debré Hospitals, 75010 Paris, France (34) Rare Disease Genomic Medicine Department, Paris Cité University, Necker Hospital for Sick Children, 75015 Paris, France (35) Department of Virology, Paris Cité University, Cochin Hospital, 75014 Paris, France (36) Division of Genetic Medicine, Department of Medicine, Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN 37232, USA (37) Department of Pathology, Microbiology, and Immunology, Vanderbilt Center for Immunobiology, Vanderbilt Institute for Infection, Immunology, and Inflammation, Vanderbilt University Medical Center, Nashville, TN 37232, USA (38) Immunology Laboratory, Necker Hospital for Sick Children, AP-HP, 75015 Paris, France (39) Inserm UMR1283, CNRS UMR8199, European Genomic Institute for Diabetes, Lille University, Lille Pasteur Institute, Lille University Hospital, 59000 Lille, France (40) Neglected Human Genetics Laboratory, Paris Cité University, 75006 Paris, France (41) Pathology Department, Ambroise-Paré Hospital, AP-HP, 92100 Boulogne-Billancourt, France (42) Department of Physiology, McGill University, Montreal, QC H3A 0G1, Canada (43) Department of Medical Microbiology, University Medical Center Utrecht, Utrecht University, 3584CX Utrecht, the Netherlands (44) College of Health and Life Sciences, Hamad Bin Khalifa University, Doha, Qatar (45) Department of Pediatric Pulmonology, Allergology and Neonatology and Biomedical Research in Endstage and Obstructive Lung Disease, German Center for Lung Research, Hannover Medical School, 30625 Hannover, Germany (46) Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, 30625 Hannover, Germany (47) Department of Human Genetics, McGill University, Montreal, QC H3A 0G1, Canada (48) Department of Pediatrics, Necker Hospital for Sick Children, AP-HP, 75015 Paris, France (49) Howard Hughes Medical Institute, New York, NY 10065, USA (50) Department of Biochemistry, McGill University, Montreal, QC H3A 0G1, Canada * Corresponding author Article History: Received 1 April 2022; Revised 22 November 2022; Accepted 19 December 2022 (miscellaneous) Published: February 2, 2023 (footnote)51 Lead contact (footnote)52 These authors contributed equally (footnote)53 These authors contributed equally (footnote)54 These authors contributed equally (footnote)55 These authors contributed equally (footnote)56 These authors contributed equally Byline: Jérémie Rosain [jeremie.rosain@institutimagine.org] (1,2,*), Anna-Lena Neehus (1,2,3,52), Jérémy Manry (1,2,2), Rui Yang (4,52), Jérémie Le Pen (5,52), Wassim Daher (6,7,52), Zhiyong Liu (4,52), Yi-Hao Chan (4,52), Natalia Tahuil (8,52), Özden Türel (9,52), Mathieu Bourgey (10,11,52), Masato Ogishi (4,52), Jean-Marc Doisne (12,13,52), Helena M. Izquierdo (14,52), Takayoshi Shirasaki (15,52), Tom Le Voyer (1,2,52), Antoine Guérin (16,17,52), Paul Bastard (1,2,4,18,52), Marcela Moncada-Vélez (4,52), Ji Eun Han (4,53), Taushif Khan (19,53), Franck Rapaport (4,53), Seon-Hui Hong (5), Andrew Cheung (5), Kathrin Haake (3), Barbara C. Mindt (20,21,22), Laura Pérez (23), Quentin Philippot (1,2), Danyel Lee (1,2,4), Peng Zhang (4), Darawan Rinchai (4), Fatima Al Ali (19), Manar Mahmoud Ahmad Ata (19), Mahbuba Rahman (19), Jessica N. Peel (4), Søren Heissel (24), Henrik Molina (24), Yasemin Kendir-Demirkol (4,25), Rasheed Bailey (4), Shuxiang Zhao (4), Jonathan Bohlen (1,2), Mathieu Mancini (10,20,21), Yoann Seeleuthner (1,2), Marie Roelens (26,27), Lazaro Lorenzo (1,2), Camille Soudée (1,2), María Elvira Josefina Paz (28), María Laura González (29), Mohamed Jeljeli (30), Jean Soulier (31,32,33), Serge Romana (34), Anne-Sophie L'Honneur (35), Marie Materna (1,2), Rubén Martínez-Barricarte (36,37), Mathieu Pochon (1,2), Carmen Oleaga-Quintas (1,2), Alexandre Michev (1,2), Mélanie Migaud (1,2), Romain Lévy (1,2,18), Marie-Alexandra Alyanakian (38), Flore Rozenberg (35), Carys A. Croft (12,13,27), Guillaume Vogt (39,40), Jean-François Emile (41), Laurent Kremer (6,7), Cindy S. Ma (16,17,54), Jörg H. Fritz (20,21,22,42,54), Stanley M. Lemon (15,54), András N. Spaan (4,43,54), Nicolas Manel (14,54), Laurent Abel (1,2,4,54), Margaret R. MacDonald (5,54), Stéphanie Boisson-Dupuis (1,2,4,55), Nico Marr (19,44,55), Stuart G. Tangye (16,17,55), James P. Di Santo (12,13,55), Qian Zhang (1,2,4,55), Shen-Ying Zhang (1,2,4,55), Charles M. Rice (5,55), Vivien Béziat (1,2,4,55), Nico Lachmann (3,45,46,55), David Langlais (10,20,47,55), Jean-Laurent Casanova [casanova@rockefeller.edu] (1,2,4,48,49,51,56,**), Philippe Gros (10,50,56), Jacinta Bustamante [jacinta.bustamante@inserm.fr] (1,2,4,26,56,***)