In this work, we provide proof of concept that the tuberculosis vaccine BCG is able to reprogram hematopoietic stem cells (HSCs), so they give place to monocytes and macrophages that are significantly more effective at clearing M.tuberculosis bacteria (Mtb). This idea –that cells of the innate immune system can acquire immunological memory independently to classical mechanisms of adaptive immunity- is commonly referred to as “trained immunity”, and constitute a major paradigm shift in recent immunology. By studying the effects of BCG in the hematopoietic precursors, instead of looking directly to the relatively shorter lived lines of effector cells (monocytes and macrophages), we demonstrate that these effects can be sustainable in vivo during longer times than previously anticipated. Our results indicate that the presence of BCG in the bone marrow niche (attained only upon intra-venous inoculation of the vaccine) triggers an expansion of the LKS sub-population of HSCs, which are polarized towards myelopoiesis, at the expense of lymphopoiesis. These effects are finally transmitted to the HSCs progeny, that give place to Monocytes and Macrophages that show specific epigenetic and transcriptomic signatures associated to an increased efficacy at eliminating Mtb bacteria upon further infection challenges, either in vivo or in vitro.
- Kaufmann*, E., Sanz*, J., Dunn*, J. L., Khan, N., Mendonça, L. E., Pacis, A., … , Barreiro, L. and Divangahi, M. (2018). BCG educates hematopoietic stem cells to generate protective innate immunity against tuberculosis. Cell, 172(1), 176-190. *=co-first author. (article)
The contents in this website are licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.