TY - JOUR
T1 - Plasminogen activator inhibitor type I may contribute to transient, non-specific changes in immunity in the subacute phase of murine tuberculosis
AU - Kager, Liesbeth M.
AU - van der Windt, Gerritje J. W.
AU - Wieland, Catharina W.
AU - Florquin, Sandrine
AU - van 't Veer, Cornelis
AU - van der Poll, Tom
PY - 2012
Y1 - 2012
N2 - 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-gamma 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. Crown Copyright (C) 2012 Published by Elsevier Masson SAS on behalf of Institut Pasteur. All rights reserved
AB - 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-gamma 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. Crown Copyright (C) 2012 Published by Elsevier Masson SAS on behalf of Institut Pasteur. All rights reserved
U2 - https://doi.org/10.1016/j.micinf.2012.03.001
DO - https://doi.org/10.1016/j.micinf.2012.03.001
M3 - Article
C2 - 22484384
SN - 1286-4579
VL - 14
SP - 748
EP - 755
JO - Microbes and infection / Institut Pasteur
JF - Microbes and infection / Institut Pasteur
IS - 9
ER -