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Publication : Human IRF1 governs macrophagic IFN-γ immunity to mycobacteria.

First Author  Rosain J Year  2023
Journal  Cell Volume  186
Issue  3 Pages  621-645.e33
PubMed ID  36736301 Mgi Jnum  J:336125
Mgi Id  MGI:7434045 Doi  10.1016/j.cell.2022.12.038
Citation  Rosain J, et al. (2023) Human IRF1 governs macrophagic IFN-gamma immunity to mycobacteria. Cell 186(3):621-645.e33
abstractText  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.
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