GSE124218
Human Bacille Calmette-Guérin vaccination elicits trained immunity via the hematopoietic progenitor compartment  [bone marrow]
Induction of trained immunity by human Bacille-Calmette-Guérin (BCG) vaccination is implicated in the beneficial heterologous effects of the vaccine, but the underlying mechanisms remain elusive. We performed global transcriptome analysis of sorted progenitors from bone marrow before (D0) and 90 days after vaccination (D90). BCG vaccination induced transcriptomic myeloid priming of the hematopoietic stem and progenitor cell (HSPC) compartment marked by the upregulation of myeloid and granulocytic pathways alongside the induction of transcription factors connected to myeloid cell function, namely Hepatocyte Nuclear Factors (HNF). These findings are corroborated by higher granulocyte numbers in BCG-vaccinated infants, HNF1-related SNP variants correlating with immune training and elevated serum levels of the HNF1 target gene SERPINA1. Taken together, we reveal a transcriptomic reprograming of HSPCs and peripheral monocytes as a trait of in vivo BCG-induced trained immunity. Overall design: mRNA profiles of sorted hematopoietic stem and progenitor cells (HSPC, i.e. pooled HSC & MPP) from human bone marrow. Sample collection was performed before and 90 days after vaccination from the same individuals (n=15 for BCG-vaccinated individuals, n=5 for placebo-treated individuals) resulting in a total of 39 transcriptomic profiles (one sample (Donor 9 D0) was identified as outlier and excluded).