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组织蛋白酶G在实验性结核病中的作用:对抗菌保护的意义及免疫治疗潜力

Cathepsin G in Experimental Tuberculosis: Relevance for Antibacterial Protection and Potential for Immunotherapy.

作者信息

Walter Kerstin, Steinwede Kathrin, Aly Sahar, Reinheckel Thomas, Bohling Jennifer, Maus Ulrich A, Ehlers Stefan

机构信息

Priority Area Infections, Research Center Borstel, Borstel 23845, Germany; German Center for Infection Research, Thematic Translational Unit Tuberculosis, partner site Borstel, Borstel 23845, Germany;

Department of Experimental Pneumology, Hannover Medical School, Hannover 30625, Germany;

出版信息

J Immunol. 2015 Oct 1;195(7):3325-33. doi: 10.4049/jimmunol.1501012. Epub 2015 Aug 28.

Abstract

Neutrophil serine proteases, such as cathepsin G (CG) and neutrophil elastase (NE), have been implicated in the protective response against infections, including experimental mycobacterial infections. The goal of this study was to explore the role of CG in immunocompetent mice challenged aerogenically with Mycobacterium tuberculosis. We used genetically CG- or CG/NE-deficient mice to define the importance of these neutrophil serine proteases for antibacterial protection, granulomatous response, and survival. In addition, we explored the effect of intratracheally delivered liposomally encapsulated CG/NE as a therapeutic approach early during M. tuberculosis infection. Our data show that the presence of CG or CG/NE prolongs survival in M. tuberculosis-infected mice. However, CG is not directly involved in antibacterial defenses, and exogenous intratracheal administration of CG combined with NE does not reduce bacterial loads in the lungs of M. tuberculosis-infected mice.

摘要

中性粒细胞丝氨酸蛋白酶,如组织蛋白酶G(CG)和中性粒细胞弹性蛋白酶(NE),已被证明在针对包括实验性分枝杆菌感染在内的感染的保护性反应中发挥作用。本研究的目的是探讨CG在经空气感染结核分枝杆菌的免疫活性小鼠中的作用。我们使用基因敲除CG或CG/NE的小鼠来确定这些中性粒细胞丝氨酸蛋白酶在抗菌保护、肉芽肿反应和生存中的重要性。此外,我们还探讨了在结核分枝杆菌感染早期,经气管内递送脂质体包裹的CG/NE作为一种治疗方法的效果。我们的数据表明,CG或CG/NE的存在可延长结核分枝杆菌感染小鼠的生存期。然而,CG并不直接参与抗菌防御,并且经气管内联合给予CG和NE并不能降低结核分枝杆菌感染小鼠肺部的细菌载量。

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