title: Mice that overexpress CC chemokine ligand 2 in their lungs show increased protective immunity to infection with Mycobacterium bovis bacille Calmette-Guérin.
abstract: BACKGROUND
  The acute phase of mycobacterial lung infection is characterized by a nearly exponential outgrowth of mycobacteria in the alveolar airspace and lung parenchymal tissue, suggesting insufficient early protective immunity against mycobacterial challenge. In the current study, we tested the hypothesis that a CC chemokine ligand 2 (CCL2)-dependent increased mononuclear phagocyte subset accumulation in distal airspaces would improve the lungs' protective immunity to infection with Mycobacterium bovis bacille Calmette-Guérin (hereafter, "M. bovis BCG").
  
  
  METHODS
  Wild-type mice and CCL2-overexpressing mice that exhibited increased pools of alveolar and lung mononuclear phagocytes-due to the lung-specific overexpression of human CCL2 in type-II alveolar epithelial cells-were infected intratracheally with M. bovis BCG and the developing lung inflammatory response was analyzed.
  
  
  RESULTS
  CCL2-overexpressing mice demonstrated significantly decreased mycobacterial loads in the bronchoalveolar space, lung parenchymal tissue, and spleen compared with wild-type mice, when both groups of mice were infected with M. bovis BCG. Moreover, in M. bovis BCG-infected mice, later-developing, accelerated resolution of lung granuloma formation was noted, particularly in CCL2-overexpressing mice as compared with wild-type mice. In addition, CCL2-overexpressing mice demonstrated an increased trafficking of mycobacteria-loaded dendritic cells towards lung-draining lymph nodes that was found to coincide with increased mycobacterial loads in this compartment.
  
  
  CONCLUSIONS
  The data of the current study suggest that CCL2-dependent amplification of endogenous host-defense programs in the lung may improve the lungs' protective immunity against mycobacterial infections.
authors.affiliation: Department of Pulmonary Medicine, Research Center Borstel, Germany.
authors.forename: Olivia
authors.initials: O
authors.lastname: Schreiber
authors.forename: Kathrin
authors.initials: K
authors.lastname: Steinwede
authors.forename: Nadine
authors.initials: N
authors.lastname: Ding
authors.forename: Mrigank
authors.initials: M
authors.lastname: Srivastava
authors.forename: Regina
authors.initials: R
authors.lastname: Maus
authors.forename: Florian
authors.initials: F
authors.lastname: Länger
authors.forename: Jana
authors.initials: J
authors.lastname: Prokein
authors.forename: Stefan
authors.initials: S
authors.lastname: Ehlers
authors.forename: Tobias
authors.initials: T
authors.lastname: Welte
authors.forename: Michael D
authors.initials: MD
authors.lastname: Gunn
authors.forename: Ulrich A
authors.initials: UA
authors.lastname: Maus
mesh_terms: D000818:Animals; D002465:Cell Movement; D018932:Chemokine CCL2 / Q000502:physiology*; D003713:Dendritic Cells / Q000502:physiology; D005260:Female; D006099:Granuloma / Q000276:immunology; D008168:Lung / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D009163:Mycobacterium bovis; D010586:Phagocytes / Q000276:immunology; D014376:Tuberculosis / Q000276:immunology*
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2