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| Status |
Public on Dec 13, 2017 |
| Title |
BCG reprogramming of hematopoietic stem cells generates protective innate immunity against tuberculosis (RNA-Seq) |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
The dogma that adaptive immunity is the only arm of the immune response with memory capacity has been recently challenged by several studies demonstrating evidence for memory-like innate immune training. However, the underlying mechanisms and location for generating such innate memory responses in vivo remains unknown. Here we show that access of Bacillus CalmetteGuérin (BCG) to the bone marrow (BM) following intravenous immunization induced local hematopoietic stem cell (HSC) expansion and enhanced myelopoiesis at the expense of lymphopoiesis. Importantly, HSC reprogramming led to the generation of epigeneticallymodified macrophages that provided significantly better protection against virulent M. tuberculosis infection than naïve macrophages. By using parabiotic and chimeric mice as well as adoptive transfer approaches, we demonstrate that training of the monocyte/macrophage lineage via BCGinduced HSC reprogramming is sustainable in vivo. Our results indicate that targeting the HSC compartment provides a novel approach for vaccine development.
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| Overall design |
Expression profiles in non-infected and MTB-infected bone marrow-derived macrophages from Control vs BCGiv vaccinated mice
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| Contributor(s) |
Kaufmann E, Dunn JL, Sanz J, Khan N, Pacis A, Tzelepis F, Pernet E, Dumaine A, Grenier J, Ahmed E, Belle J, Besla R, Mazer B, King IL, Nijnik A, Barreiro LB, Divangahi M |
| Citation(s) |
29328912 |
| Submission date |
May 05, 2017 |
| Last update date |
Jul 25, 2021 |
| Contact name |
Luis Barreiro |
| E-mail(s) |
lbarreiro@uchicago.edu
|
| Organization name |
University of Chicago
|
| Street address |
900 E 57th Street
|
| City |
Chicago |
| State/province |
Illinois |
| ZIP/Postal code |
60637 |
| Country |
USA |
| |
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| Platforms (2) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
|
| Samples (32)
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| This SubSeries is part of SuperSeries: |
| GSE98600 |
BCG reprogramming of hematopoietic stem cells generates protective innate immunity against tuberculosis |
|
| Relations |
| BioProject |
PRJNA385677 |
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