Human IRF1 governs macrophagic IFN-γ immunity to mycobacteria.
IRF1
Mycobacterium
inborn errors of immunity
interferon-stimulated gene
interferon-γ
macrophages
viruses
Journal
Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066
Informations de publication
Date de publication:
02 02 2023
02 02 2023
Historique:
received:
01
04
2022
revised:
22
11
2022
accepted:
19
12
2022
entrez:
3
2
2023
pubmed:
4
2
2023
medline:
8
2
2023
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 36736301
pii: S0092-8674(22)01581-1
doi: 10.1016/j.cell.2022.12.038
pmc: PMC9907019
mid: NIHMS1860716
pii:
doi:
Substances chimiques
Interferon-gamma
82115-62-6
Interferon-alpha
0
IRF1 protein, human
0
Interferon Regulatory Factor-1
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
621-645.e33Subventions
Organisme : NHGRI NIH HHS
ID : UM1 HG006504
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI091707
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001866
Pays : United States
Organisme : NIH HHS
ID : S10 OD018521
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI162568
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI088364
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI163029
Pays : United States
Organisme : NHGRI NIH HHS
ID : U24 HG008956
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI095983
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI103083
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI150095
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States
Organisme : CIHR
Pays : Canada
Informations de copyright
Crown Copyright © 2022. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests J.-L.C. serves on the scientific advisory boards of ADMA Biologics Inc., Kymera Therapeutics, and Elixiron Immunotherapeutics.
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