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| Status |
Public on Jan 12, 2023 |
| Title |
Human IRF1 governs phagocytic IFN-γ immunity to mycobacteria but not cell-intrinsic IFN-a/b immunity to viruses [scRNAseq] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Inborn errors of human IFN-γ immunity underlie mycobacterial diseases, while inborn errors of IFN-a/b immunity underlie viral diseases. Both types of IFNs induce the transcription factor IRF1. We describe two unrelated children with inherited complete IRF1 deficiency and early-onset, multiple, life-threatening diseases caused by weakly virulent mycobacteria. They have no history of severe viral disease, despite exposure to many viruses, including SARS-CoV-2 that is life-threatening in individuals with deficient IFN-a/b. There is a much greater IRF1-dependent response to IFN-γ than IFN-a/b in vitro, both quantitatively and qualitatively. Monocyte-derived macrophages and iPSC-derived macrophages of both patients do not upregulate at least 40% of target genes normally induced by IFN-γ. In contrast, cell-intrinsic IFN-a/b immunity to a wide range of viruses, including HIV and SARS-CoV-2, is maintained. Human IRF1 is thus largely redundant for antiviral IFN-a/b immunity across cell types. By contrast, human IRF1 is essential for IFN-γ immunity to mycobacteria in mononuclear myeloid cells.
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| Overall design |
To investigate the impact of IRF1 loss-of-function on the development of immune cells and their transcriptional program, we have performed scRNA-seq on PBMC from 1 pediatric IRF1 deficient patient (P1.1). This dataset has been combined with CITE-seq for a second sample obtained for this patient (P1.2) and a second IRF1 deficient patient (P2), together with healthy controls. To investigate the impact of IRF1 loss-of-function on the development of immune cells and their transcriptional program, we have performed scRNA-seq on PBMC from 1 pediatric IRF1 deficient patient. This dataset has been combined with CITE-seq for a second sample obtained for this patient and a second IRF1 deficient patient, together with healthy controls.
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| Contributor(s) |
Langlais D, Mancini M, Bourgey M, Rosain J, Gros P, Casanova J, Bustamante J |
| Citation(s) |
36736301 |
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| Submission date |
Oct 24, 2022 |
| Last update date |
Mar 02, 2023 |
| Contact name |
David Langlais |
| E-mail(s) |
david.langlais@mcgill.ca
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| Organization name |
McGill University
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| Department |
Human Genetics
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| Lab |
Inflammation Genomics Lab
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| Street address |
740 Ave Dr Penfield, rm 4203, McGill Genome Centre
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| City |
MONTREAL |
| State/province |
QC |
| ZIP/Postal code |
H3A0G1 |
| Country |
Canada |
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| Platforms (1) |
| GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
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| Samples (2) |
| GSM6674754 |
Patient P1.1, mRNA-derived cDNA, scRNA-seq (capture reaction 1of2) |
| GSM6674755 |
Patient P1.1, mRNA-derived cDNA, scRNA-seq (capture reaction 2of2) |
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| This SubSeries is part of SuperSeries: |
| GSE216489 |
Human IRF1 governs phagocytic IFN-γ immunity to mycobacteria but not cell-intrinsic IFN-a/b immunity to viruses |
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| Relations |
| BioProject |
PRJNA893695 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE216486_RAW.tar |
15.5 Mb |
(http)(custom) |
TAR (of MTX, TSV) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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