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BCG reprogramming of hematopoietic stem cells generates protective innate immunity against tuberculosis (RNA-Seq)

GSE98599 Mus musculus Expression profiling by high throughput sequencing 32 samples Submitted 2017/12/13 Platform GPL17021Platform GPL21103
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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Also filed as BioProject PRJNA385677 and SRA study SRP106570. Searching any of these in the dataset finder brings you back here.

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