title: Macrophages play a dual role during pulmonary tuberculosis in mice.
abstract: Pulmonary macrophages provide the preferred hiding and replication site of Mycobacterium tuberculosis but display antimicrobial functions. This raises questions regarding the role of macrophages during tuberculosis. We depleted lungs of activated macrophages (activated macrophage(-) mice) and compared this with nonselective macrophage depletion (macrophage(-) mice). Although nonselective depletion of macrophages after infection improved clinical outcome, depletion of activated macrophages led to impaired resistance, reflected by enhanced mycobacterial outgrowth. The production of tumor necrosis factor- alpha and numbers of granuloma decreased after depletion of activated macrophages. Both macrophage(-) and activated macrophage(-) mice showed polarized production of interferon- gamma by splenocytes and lymph-node cells and were able to attract and activate T cells in the lung. These data demonstrate that the dual role of macrophages is associated with the activation state of macrophages and that extensive apoptosis found in patients with tuberculosis could be part of a host defense strategy, as long as these cells are not activated.
authors.affiliation: Laboratory of Experimental Internal Medicine, Department of Infectious Diseases, Tropical Medicine and AIDS, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands. j.c.leemans@amc.uva.nl
authors.forename: Jaklien C
authors.initials: JC
authors.lastname: Leemans
authors.forename: Theo
authors.initials: T
authors.lastname: Thepen
authors.forename: Sebastiaan
authors.initials: S
authors.lastname: Weijer
authors.forename: Sandrine
authors.initials: S
authors.lastname: Florquin
authors.forename: Nico
authors.initials: N
authors.lastname: van Rooijen
authors.forename: Jan G
authors.initials: JG
authors.lastname: van de Winkel
authors.forename: Tom
authors.initials: T
authors.lastname: van der Poll
mesh_terms: D000818:Animals; D017209:Apoptosis; D005260:Female; D006099:Granuloma; D007371:Interferon-gamma / Q000032:analysis; D008168:Lung / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation; D008262:Macrophage Activation; D016676:Macrophages, Alveolar / Q000276:immunology* / Q000382:microbiology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009169:Mycobacterium tuberculosis / Q000254:growth & development / Q000276:immunology*; D017452:Receptors, IgG / Q000032:analysis; D013154:Spleen / Q000276:immunology / Q000382:microbiology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014397:Tuberculosis, Pulmonary / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D017452:Receptors, IgG; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma