Mycobacterium tuberculosis-Infected Hematopoietic Stem and Progenitor Cells Unable to Express Inducible Nitric Oxide Synthase Propagate Tuberculosis in Mice. (17th February 2018)

• Record Type: Journal Article
• Authors: Reece, Stephen T; Vogelzang, Alexis; Tornack, Julia; Bauer, Wolfgang; Zedler, Ulrike; Schommer-Leitner, Sandra; Stingl, Georg; Melchers, Fritz; Kaufmann, Stefan H E
• Is Part Of: Journal of infectious diseases. Volume 217:Number 10(2018)
• Page Start: 1667
• Page End: 1671
• Publication Date: 2018-02-17
• Subjects: inducible nitric oxide synthase -- hematopoietic stem and progenitor cells -- Mycobacterium tuberculosis; Communicable diseases -- Periodicals; Diseases -- Causes and theories of causation -- Periodicals; Medicine -- Periodicals; Communicable Diseases -- Periodicals; Electronic journals; 616.9
• DOI: 10.1093/infdis/jiy041
• Languages: English
• ISSNs: 0022-1899

Abstract

Abstract : We show that bone marrow stem and progenitor cells containing Mycobacterium tuberculosis induce hallmarks of tuberculosis if killing of intracellular bacteria is defective. Understanding the relative contribution of these cells in tuberculosis latency and reactivation could inform novel host-directed therapies. 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.