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 CalmetteGurin (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 nave 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. SOURCE: Luis Barreiro (lbbarreiro@gmail.com) - Barreiro Lab CHU Sainte-Justine Research Center

Pluto Bioinformatics

GSE98599: BCG reprogramming of hematopoietic stem cells generates protective innate immunity against tuberculosis (RNA-Seq)