title: Lung-residing myeloid-derived suppressors display dual functionality in murine pulmonary tuberculosis.
abstract: BACKGROUND
  Myeloid cells encompass distinct populations with unique functions during homeostasis and disease. Recently, a novel subset of innate cells, myeloid-derived suppressor cells (MDSCs), has been described in cancer, which suppresses T-cell responses and fosters disease progression. The role of MDSCs in infection is insufficiently addressed.
  
  
  OBJECTIVE
  To examine the presence and function of MDSCs during experimental pulmonary tuberculosis (TB) and further understand the immunologic consequences of direct interactions between MDSCs and lung bacterial pathogens.
  
  
  METHODS
  Using cell-based approaches and experimental mouse models for pulmonary TB we characterized MDSCs as novel myeloid populations directly interacting with Mycobacterium tuberculosis (Mtb).
  
  
  RESULTS
  MDSCs readily phagocytosed Mtb, and released proinflammatory (IL-6, IL-1α) and immunomodulatory (IL-10) cytokines while retaining their suppressive capacity. MDSCs were identified at the site of infection in the lung in disease-resistant and -susceptible mice during pulmonary TB. Excessive MDSC accumulation in lungs correlated with elevated surface expression of IL-4Rα and heightened TB lethality, whereas targeted depletion of MDSCs ameliorated disease.
  
  
  CONCLUSIONS
  Our data reveal that MDSCs provide a niche for pathogen survival and tailor immunity in TB. These findings suggest MDSCs as amenable targets for host-directed therapies and emphasize them as cellular-immune regulators during chronic inflammatory conditions, including chronic infections and microbial complications of neoplastic disorders.
authors.affiliation: 1 Department of Immunology.
authors.forename: Julia K
authors.initials: JK
authors.lastname: Knaul
authors.forename: Sabine
authors.initials: S
authors.lastname: Jörg
authors.forename: Dagmar
authors.initials: D
authors.lastname: Oberbeck-Mueller
authors.forename: Ellen
authors.initials: E
authors.lastname: Heinemann
authors.forename: Lisa
authors.initials: L
authors.lastname: Scheuermann
authors.forename: Volker
authors.initials: V
authors.lastname: Brinkmann
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Mollenkopf
authors.forename: Vladimir
authors.initials: V
authors.lastname: Yeremeev
authors.forename: Stefan H E
authors.initials: SH
authors.lastname: Kaufmann
authors.forename: Anca
authors.initials: A
authors.lastname: Dorhoi
mesh_terms: D000818:Animals; D051379:Mice; D008810:Mice, Inbred C57BL; D022423:Myeloid Cells / Q000502:physiology*; D014397:Tuberculosis, Pulmonary / Q000276:immunology*
keywords: Mycobacterium tuberculosis; immune suppression; inflammation; myeloid-derived suppressor cells