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: Liesbeth M Kager, Gerritje J W van der Windt, Catharina W Wieland, Sandrine Florquin, Cornelis van 't Veer, Tom van der Poll
• Journal: Microbes and infection (Microbes Infect) Vol. 14 Issue 9 Pg. 748-55 (Aug 2012) ISSN: 1769-714X [Electronic] France
• PMID: 22484384 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Crown Copyright © 2012. Published by Elsevier Masson SAS. All rights reserved.

Chemical References

• Cytokines
• Plasminogen Activator Inhibitor 1

Topics

• Animals
• Bacterial Load
• Cytokines (metabolism)
• Disease Models, Animal
• Lung (microbiology, pathology)
• Lymphocytes (immunology)
• Macrophages (immunology)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Mycobacterium tuberculosis (immunology)
• Plasminogen Activator Inhibitor 1 (deficiency, immunology)
• Tuberculosis (immunology)