Plasminogen activator inhibitor type I may contribute to transient, non-specific changes in immunity in the subacute phase of murine tuberculosis

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• 作者：Liesbeth M. Kager ; Gerritje J.W. van der Windt ; Catharina W. Wiel ; S ; rine Florquin ; Cornelis van ¡¯t Veer ; Tom van der Poll
• 关键词：Tuberculosis ; Inflammation ; Immunity ; Fibrinolysis ; Plasminogen activator inhibitor type 1 (PAI-1)
• 刊名：Microbes and Infection
• 出版年：2012
• 出版时间：August, 2012
• 年：2012
• 卷：14
• 期：9
• 页码：748-755
• 全文大小：1239 K

文摘

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-¦Ã 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.