title: Cathepsin G in Experimental Tuberculosis: Relevance for Antibacterial Protection and Potential for Immunotherapy.
abstract: Neutrophil serine proteases, such as cathepsin G (CG) and neutrophil elastase (NE), have been implicated in the protective response against infections, including experimental mycobacterial infections. The goal of this study was to explore the role of CG in immunocompetent mice challenged aerogenically with Mycobacterium tuberculosis. We used genetically CG- or CG/NE-deficient mice to define the importance of these neutrophil serine proteases for antibacterial protection, granulomatous response, and survival. In addition, we explored the effect of intratracheally delivered liposomally encapsulated CG/NE as a therapeutic approach early during M. tuberculosis infection. Our data show that the presence of CG or CG/NE prolongs survival in M. tuberculosis-infected mice. However, CG is not directly involved in antibacterial defenses, and exogenous intratracheal administration of CG combined with NE does not reduce bacterial loads in the lungs of M. tuberculosis-infected mice.
authors: Priority Area Infections, Research Center Borstel, Borstel 23845, Germany; German Center for Infection Research, Thematic Translational Unit Tuberculosis, partner site Borstel, Borstel 23845, Germany; kwalter@fz-borstel.de.
authors: Kerstin
authors: K
authors: Walter
authors: Department of Experimental Pneumology, Hannover Medical School, Hannover 30625, Germany;
authors: Kathrin
authors: K
authors: Steinwede
authors: Medical Clinic for Infection Biology and Pneumology, Charité University Medicine Berlin, Berlin 13353, Germany; and.
authors: Sahar
authors: S
authors: Aly
authors: Institute of Molecular Medicine and Cell Research, University of Freiburg, Freiburg 79104, Germany.
authors: Thomas
authors: T
authors: Reinheckel
authors: Department of Experimental Pneumology, Hannover Medical School, Hannover 30625, Germany;
authors: Jennifer
authors: J
authors: Bohling
authors: Department of Experimental Pneumology, Hannover Medical School, Hannover 30625, Germany;
authors: Ulrich A
authors: UA
authors: Maus
authors: Priority Area Infections, Research Center Borstel, Borstel 23845, Germany; German Center for Infection Research, Thematic Translational Unit Tuberculosis, partner site Borstel, Borstel 23845, Germany;
authors: Stefan
authors: S
authors: Ehlers
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents; D056649:Cathepsin G / Q000235:genetics* / Q000627:therapeutic use; D007167:Immunotherapy; D019272:Leukocyte Elastase / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology; D014376:Tuberculosis / Q000276:immunology* / Q000382:microbiology / Q000628:therapy*
chemical_list: D000900:Anti-Bacterial Agents; D056649:Cathepsin G; D019272:Leukocyte Elastase