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Series GSE156135 Query DataSets for GSE156135
Status Public on Aug 13, 2020
Title M. tuberculosis reprograms HSCs to limit myelopoiesis and impair trained immunity via a type I IFN/iron axis [AERO_SERIES_2]
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary A greater understanding of hematopoietic stem cell (HSC) regulation is required for dissecting protective versus detrimental immunity to pathogens that cause chronic infections such as Mycobacterium tuberculosis (Mtb). We have shown that systemic administration of BCG or b-glucan reprograms HSCs in the BM via a type II interferon (IFN-II) or IL1 response, respectively, that confers protective trained immunity against Mtb. Yet, whether BCG/β-Glucan is unique in its ability to induce this protection remains unknown. Herein, we demonstrate that unlike BCG or b-glucan, Mtb reprograms HSCs via IFN-I response that suppresses myelopoiesis and impairs protective trained immunity to Mtb. Mechanistically, IFN-I response dysregulates iron metabolism, depolarizes mitochondrial membrane potential, and induces cell death in myeloid progenitors. Finally, activation of IFN-I/iron axis in myeloid progenitors generates a detrimental trained immunity to Mtb infection. These results identify an unanticipated immune evasion strategy of Mtb in the bone marrow that controls the magnitude and anti-microbial capacity of innate immunity to infection
 
Overall design Single cell RNA expression profiles of LKS+, and cKit+ progenitor cells of Control mice, and mice subject to an aerosol challenge with M.tuberculosis.
 
Contributor(s) Khan N, Downey J, Sanz J, Kaufmann E, Blankenhaus B, Pacis A, Pernet E, Ahmed E, Cardoso S, Nijnik A, Mazer B, Sassetti C, Behr MA, Soares MP, Barreiro LB, Divangahi M
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Submission date Aug 12, 2020
Last update date Aug 15, 2020
Contact name Saideep Gona
E-mail(s) gona.saideep1@gmail.com
Organization name University of Chicago
Street address 1000 E 53rd St
City Chicago
State/province IL - Illinois
ZIP/Postal code 60615
Country USA
 
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (4)
GSM4725214 AERO_SERIES_2: LKS_PBS
GSM4725215 AERO_SERIES_2: LKS_MTB
GSM4725216 AERO_SERIES_2: PROG_PBS
This SubSeries is part of SuperSeries:
GSE156137 M. tuberculosis reprograms HSCs to limit myelopoiesis and impair trained immunity via a type I IFN/iron axis
Relations
BioProject PRJNA656830
SRA SRP277239

Download family Format
SOFT formatted family file(s) SOFTHelp
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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE156135_RAW.tar 213.9 Mb (http)(custom) TAR (of MTX, TSV)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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