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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 [CITEseq] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
Other
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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) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (10)
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| GSM6674767 |
Adult Healthy Control 1, ADT-derived cDNA |
| GSM6674768 |
Adult Healthy Control 2, mRNA-derived cDNA |
| GSM6674769 |
Adult Healthy Control 2, ADT-derived cDNA |
| GSM6674770 |
Pediatric Healthy Control 1, mRNA-derived cDNA |
| GSM6674771 |
Pediatric Healthy Control 1, ADT-derived cDNA |
| GSM6674772 |
Patient P2, mRNA-derived cDNA |
| GSM6674773 |
Patient P2, ADT-derived cDNA |
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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 |
PRJNA893694 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE216488_IRF1-02-MM-GEX_LAN1403A4-1_IRF1-02-MM-CSP_LAN1403A6-1_filtered_barcodes.tsv.gz |
46.2 Kb |
(ftp)(http) |
TSV |
| GSE216488_IRF1-02-MM-GEX_LAN1403A4-1_IRF1-02-MM-CSP_LAN1403A6-1_filtered_features.tsv.gz |
326.0 Kb |
(ftp)(http) |
TSV |
| GSE216488_IRF1-02-MM-GEX_LAN1403A4-1_IRF1-02-MM-CSP_LAN1403A6-1_filtered_matrix.mtx.gz |
52.7 Mb |
(ftp)(http) |
MTX |
| GSE216488_PED-CONT-MM-GEX_LAN1403A3-1_PED-CONT-MM-CSP_LAN1403A5-1_filtered_barcodes.tsv.gz |
22.8 Kb |
(ftp)(http) |
TSV |
| GSE216488_PED-CONT-MM-GEX_LAN1403A3-1_PED-CONT-MM-CSP_LAN1403A5-1_filtered_features.tsv.gz |
326.0 Kb |
(ftp)(http) |
TSV |
| GSE216488_PED-CONT-MM-GEX_LAN1403A3-1_PED-CONT-MM-CSP_LAN1403A5-1_filtered_matrix.mtx.gz |
39.0 Mb |
(ftp)(http) |
MTX |
| GSE216488_RAW.tar |
312.3 Mb |
(http)(custom) |
TAR (of MTX, TSV) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
| Processed data are available on Series record |
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