Diagenode

BCG Educates Hematopoietic Stem Cells to Generate Protective Innate Immunity against Tuberculosis.


Kaufmann E, Sanz J, Dunn JL, Khan N, Mendonça LE, Pacis A, Tzelepis F, Pernet E, Dumaine A, Grenier JC, Mailhot-Léonard F, Ahmed E, Belle J, Besla R, Mazer B, King IL, Nijnik A, Robbins CS, Barreiro LB, Divangahi M

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 remain unknown. Here, we show that access of Bacillus Calmette-Guérin (BCG) to the bone marrow (BM) changes the transcriptional landscape of hematopoietic stem cells (HSCs) and multipotent progenitors (MPPs), leading to local cell expansion and enhanced myelopoiesis at the expense of lymphopoiesis. Importantly, BCG-educated HSCs generate epigenetically modified macrophages that provide 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 BCG-induced HSC reprogramming is sustainable in vivo. Our results indicate that targeting the HSC compartment provides a novel approach for vaccine development.

Tags
Microplex Library Preparation kit

Share this article

Published
January, 2018

Source

Products used in this publication

  • ChIP kit icon
    C05010012
    MicroPlex Library Preparation Kit v2 (12 indexes)

活动

  • AACR 2024
    San Diego, California, USA
    Apr 5-Apr 10, 2024
 查看所有活动

新闻

 查看所有新闻


The European Regional Development Fund and Wallonia are investing in your future.

Extension of industrial buildings and new laboratories.


       Site map   |   Contact us   |   Conditions of sales   |   Conditions of purchase   |   Privacy policy   |   Diagenode Diagnostics