Mycobacterium tuberculosis infection drives differential responses in the bone marrow hematopoietic stem and progenitor cells

Infect Immun. 2023 Oct 17;91(10):e0020123. doi: 10.1128/iai.00201-23. Epub 2023 Sep 27.


Hematopoietic stem and progenitor cells (HSPCs) play a vital role in the host response to infection through the rapid and robust production of mature immune cells. These HSPC responses can be influenced, directly and indirectly, by pathogens as well. Infection with Mycobacterium tuberculosis (Mtb) can drive lymphopoiesis through modulation of type I interferon (IFN) signaling. We have previously found that the presence of a drug resistance (DR)-conferring mutation in Mtb drives altered host-pathogen interactions and heightened type I IFN production in vitro. But the impacts of this DR mutation on in vivo host responses to Mtb infection, particularly the hematopoietic compartment, remain unexplored. Using a mouse model, we show that, while drug-sensitive Mtb infection induces expansion of HSPC subsets and a skew toward lymphopoiesis, DR Mtb infection fails to induce an expansion of these subsets and an accumulation of mature granulocytes in the bone marrow. Using single-cell RNA sequencing, we show that the HSCs from DR Mtb-infected mice fail to upregulate pathways related to cytokine signaling across all profiled HSC subsets. Collectively, our studies report a novel finding of a chronic infection that fails to induce a potent hematopoietic response that can be further investigated to understand pathogen-host interaction at the level of hematopoiesis.

Keywords: Mycobacterium tuberculosis; hematopoiesis; infectious disease; stem cells.

MeSH terms

  • Bacterial Infections* / metabolism
  • Bone Marrow
  • Bone Marrow Cells
  • Hematopoiesis / physiology
  • Hematopoietic Stem Cells
  • Humans
  • Mycobacterium tuberculosis* / physiology
  • Tuberculosis*