Mycobacterium tuberculosis-Infected Hematopoietic Stem and Progenitor Cells Unable to Express Inducible Nitric Oxide Synthase Propagate Tuberculosis in Mice

J Infect Dis. 2018 Apr 23;217(10):1667-1671. doi: 10.1093/infdis/jiy041.

Abstract

Persistence of Mycobacterium tuberculosis within human bone marrow stem cells has been identified as a potential bacterial niche during latent tuberculosis. Using a murine model of tuberculosis, we show here that bone marrow stem and progenitor cells containing M. tuberculosis propagated tuberculosis when transferred to naive mice, given that both transferred cells and recipient mice were unable to express inducible nitric oxide synthase, which mediates killing of intracellular bacteria via nitric oxide. Our findings suggest that bone marrow stem and progenitor cells containing M. tuberculosis propagate hallmarks of disease if nitric oxide-mediated killing of bacteria is defective.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Hematopoietic Stem Cell Transplantation / methods
  • Hematopoietic Stem Cells / metabolism*
  • Hematopoietic Stem Cells / microbiology*
  • Mice
  • Mice, Inbred C57BL
  • Mycobacterium tuberculosis / pathogenicity*
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type II / metabolism*
  • Stem Cells / metabolism*
  • Stem Cells / microbiology*
  • Tuberculosis / metabolism*
  • Tuberculosis / microbiology

Substances

  • Nitric Oxide
  • Nitric Oxide Synthase Type II