Human IRF1 governs macrophagic IFN-γ immunity to mycobacteria.

Human IRF1 governs macrophagic IFN-γ immunity to mycobacteria.

Rosain J,Neehus A,Manry J,Yang R,Le Pen J,Daher W,Liu Z,Chan Y,Tahuil N,Türel Ö,Bourgey M,Ogishi M,Doisne J,Izquierdo H,Shirasaki T,Le Voyer T,Guérin A,Bastard P,Moncada-Vélez M,Han J,Khan T,Rapaport F,Hong S,Cheung A,Haake K,Mindt B,Pérez L,Philippot Q,Lee D,Zhang P,Rinchai D,Al Ali F,Ahmad Ata M,Rahman M,Peel J,Heissel S,Molina H,Kendir-Demirkol Y,Bailey R,Zhao S,Bohlen J,Mancini M,Seeleuthner Y,Roelens M,Lorenzo L,Soudée C,Paz M,González M,Jeljeli M,Soulier J,Romana S,L'Honneur A,Materna M,Martínez-Barricarte R,Pochon M,Oleaga-Quintas C,Michev A,Migaud M,Lévy R,Alyanakian M,Rozenberg F,Croft C,Vogt G,Emile J,Kremer L,Ma C,Fritz J,Lemon S,Spaan A,Manel N,Abel L,MacDonald M,Boisson-Dupuis S,Marr N,Tangye S,Di Santo J,Zhang Q,Zhang S,Rice C,Béziat V,Lachmann N,Langlais D,Casanova J,Gros P,Bustamante J

Source :

2023 Fév 3

Pmid / DOI:

36736301

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.KEYWORDSIRF1, Mycobacterium, inborn errors of immunity, interferon-stimulated gene, interferon-γ, macrophages, virusesCrown Copyright © 2022. Published by Elsevier Inc. All rights reserved.

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