Human IRF1 governs macrophagic IFN-γ immunity to mycobacteria
Publication date
2023-02-02
Authors
Rosain, Jérémie
Neehus, Anna-Lena
Manry, Jérémy
Yang, Rui
Le Pen, Jérémie
Daher, Wassim
Liu, Zhiyong
Chan, Yi-Hao
Tahuil, Natalia
Türel, Özden
Editors
Advisors
Supervisors
Document Type
Article
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Abstract
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.
Keywords
COVID-19, Child, Humans, Interferon Regulatory Factor-1, Interferon-alpha, Interferon-gamma, Mycobacterium, SARS-CoV-2, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't
Citation
Rosain, J, Neehus, A-L, Manry, J, Yang, R, Le Pen, J, Daher, W, Liu, Z, Chan, Y-H, Tahuil, N, Türel, Ö, Bourgey, M, Ogishi, M, Doisne, J-M, Izquierdo, H M, Shirasaki, T, Le Voyer, T, Guérin, A, Bastard, P, Moncada-Vélez, M, Han, J E, Khan, T, Rapaport, F, Hong, S-H, Cheung, A, Haake, K, Mindt, B C, Pérez, L, Philippot, Q, Lee, D, Zhang, P, Rinchai, D, Al Ali, F, Ahmad Ata, M M, Rahman, M, Peel, J N, Heissel, S, Molina, H, Kendir-Demirkol, Y, Bailey, R, Zhao, S, Bohlen, J, Seeleuthner, Y, Roelens, M, Lorenzo, L, Soudée, C, Paz, M E J, González, M L, Jeljeli, M, Soulier, J, Romana, S, L'Honneur, A-S, Materna, M, Martínez-Barricarte, R, Pochon, M, Oleaga-Quintas, C, Michev, A, Migaud, M, Lévy, R, Alyanakian, M-A, Rozenberg, F, Croft, C A, Vogt, G, Emile, J-F, Kremer, L, Ma, C S, Fritz, J H, Lemon, S M, Spaan, A N, Manel, N, Abel, L, MacDonald, M R, Boisson-Dupuis, S, Marr, N, Tangye, S G, Di Santo, J P, Zhang, Q, Zhang, S-Y, Rice, C M, Béziat, V, Lachmann, N, Langlais, D, Casanova, J-L, Gros, P & Bustamante, J 2023, 'Human IRF1 governs macrophagic IFN-γ immunity to mycobacteria', Cell, vol. 186, no. 3, pp. 621-645.e33. https://doi.org/10.1016/j.cell.2022.12.038