title: Plasminogen activator inhibitor type I may contribute to transient, non-specific changes in immunity in the subacute phase of murine tuberculosis.
abstract: Tuberculosis, caused by Mycobacterium (M.) tuberculosis, is a devastating infectious disease causing many deaths worldwide. Non-specific host defense mechanisms such as the coagulation and fibrinolytic system may give insight in possible new therapeutic targets. Plasminogen activator inhibitor type-1 (PAI-1), an important regulator of inflammation and fibrinolysis, might be of interest as tuberculosis patients have elevated plasma levels of PAI-1. In this study we set out to investigate the role of PAI-1 during tuberculosis in vivo. Wildtype (WT) and PAI-1 deficient (PAI-1⁻/⁻) mice were intranasally infected with M. tuberculosis H37rv and sacrificed after 2, 5 and 29 weeks. Five weeks post-infection, bacterial loads in lungs of PAI-1⁻/⁻ mice were significantly higher compared to WT mice, while no differences were seen 2 and 29 weeks post-infection. At two weeks post-infection increased influx of macrophages and lymphocytes was observed. PAI-1 deficiency was associated with a reduced cytokine response in the lungs; however, upon stimulation with tuberculin purified protein derivative (PPD), PAI-1⁻/⁻ splenocytes released increased levels of IFN-γ compared to WT. No clear differences were found between PAI-1⁻/⁻ and WT mice at 29 weeks after infection. In conclusion, these data suggest that PAI-1 contributes to transient, non-specific changes in immunity during the early phase of murine tuberculosis.
authors.affiliation: Center for Infection and Immunity Amsterdam-CINIMA, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. l.m.kager@amc.uva.nl
authors.forename: Liesbeth M
authors.initials: LM
authors.lastname: Kager
authors.forename: Gerritje J W
authors.initials: GJ
authors.lastname: van der Windt
authors.forename: Catharina W
authors.initials: CW
authors.lastname: Wieland
authors.forename: Sandrine
authors.initials: S
authors.lastname: Florquin
authors.forename: Cornelis
authors.initials: C
authors.lastname: van 't Veer
authors.forename: Tom
authors.initials: T
authors.lastname: van der Poll
mesh_terms: D000818:Animals; D058491:Bacterial Load; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D008168:Lung / Q000382:microbiology / Q000473:pathology; D008214:Lymphocytes / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D017395:Plasminogen Activator Inhibitor 1 / Q000172:deficiency / Q000276:immunology*; D014376:Tuberculosis / Q000276:immunology*
chemical_list: D016207:Cytokines; D017395:Plasminogen Activator Inhibitor 1