title: Human and Mouse Hematopoietic Stem Cells Are a Depot for Dormant Mycobacterium tuberculosis.
abstract: An estimated third of the world's population is latently infected with Mycobacterium tuberculosis (Mtb), with no clinical signs of tuberculosis (TB), but lifelong risk of reactivation to active disease. The niches of persisting bacteria during latent TB infection remain unclear. We detect Mtb DNA in peripheral blood selectively in long-term repopulating pluripotent hematopoietic stem cells (LT-pHSCs) as well as in mesenchymal stem cells from latently infected human donors. In mice infected with low numbers of Mtb, that do not develop active disease we, again, find LT-pHSCs selectively infected with Mtb. In human and mouse LT-pHSCs Mtb are stressed or dormant, non-replicating bacteria. Intratracheal injection of Mtb-infected human and mouse LT-pHSCs into immune-deficient mice resuscitates Mtb to replicating bacteria within the lung, accompanied by signs of active infection. We conclude that LT-pHSCs, together with MSCs of Mtb-infected humans and mice serve as a hitherto unappreciated quiescent cellular depot for Mtb during latent TB infection.
authors.affiliation: Senior Group on Lymphocyte Development, Max Planck Institute for Infection Biology, Berlin, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Tornack
authors.affiliation: Department of Immunology, Max Planck Institute for Infection Biology, Berlin, Germany.
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Reece
authors.affiliation: Division of Immunology, Allergy and Infectious Diseases, Department of Dermatology, Medical University of Vienna, Vienna, Austria.
authors.forename: Wolfgang M
authors.identifier: http://orcid.org/0000-0002-0155-1176
authors.initials: WM
authors.lastname: Bauer
authors.affiliation: Department of Immunology, Max Planck Institute for Infection Biology, Berlin, Germany.
authors.forename: Alexis
authors.initials: A
authors.lastname: Vogelzang
authors.affiliation: Department of Immunology, Max Planck Institute for Infection Biology, Berlin, Germany.
authors.forename: Silke
authors.initials: S
authors.lastname: Bandermann
authors.affiliation: Department of Immunology, Max Planck Institute for Infection Biology, Berlin, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Zedler
authors.affiliation: Division of Immunology, Allergy and Infectious Diseases, Department of Dermatology, Medical University of Vienna, Vienna, Austria.
authors.forename: Georg
authors.initials: G
authors.lastname: Stingl
authors.affiliation: Department of Immunology, Max Planck Institute for Infection Biology, Berlin, Germany.
authors.forename: Stefan H E
authors.initials: SH
authors.lastname: Kaufmann
authors.affiliation: Senior Group on Lymphocyte Development, Max Planck Institute for Infection Biology, Berlin, Germany.
authors.forename: Fritz
authors.initials: F
authors.lastname: Melchers
mesh_terms: D000328:Adult; D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D001854:Bone Marrow Cells / Q000378:metabolism; D002469:Cell Separation; D005260:Female; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000382:microbiology*; D006801:Humans; D055985:Latent Tuberculosis / Q000382:microbiology*; D008168:Lung / Q000382:microbiology; D008297:Male; D059630:Mesenchymal Stem Cells / Q000382:microbiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D009169:Mycobacterium tuberculosis; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1 / Q000378:metabolism; D055815:Young Adult
chemical_list: D018952:Antigens, CD34; C000604062:Slamf1 protein, mouse; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1