Human IRF1 governs macrophagic IFN-γ immunity to mycobacteria

Creative Commons License

Rosain J., Neehus A., Manry J., Yang R., Le Pen J., Daher W., ...Daha Fazla

Cell, cilt.186, sa.3, ss.621, 2023 (SCI-Expanded, Scopus) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 186 Sayı: 3
  • Basım Tarihi: 2023
  • Doi Numarası: 10.1016/j.cell.2022.12.038
  • Dergi Adı: Cell
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, CAB Abstracts, Chemical Abstracts Core, EMBASE, MEDLINE, Veterinary Science Database, DIALNET
  • Sayfa Sayıları: ss.621
  • Anahtar Kelimeler: inborn errors of immunity, interferon-stimulated gene, interferon-γ, IRF1, macrophages, Mycobacterium, viruses
  • Açık Arşiv Koleksiyonu: AVESİS Açık Erişim Koleksiyonu
  • Bezmiâlem Vakıf Üniversitesi Adresli: Evet

Özet

© 2022Inborn 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.