Cathepsin L protects mice from mycoplasmal infection and is essential for airway lymphangiogenesis.
Cathepsin L protects mice from mycoplasmal infection and is essential for airway lymphangiogenesis.
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组织蛋白酶 L 可以保护小鼠免受支原体感染，并且对于气道淋巴管生成至关重要。
DOI：
10.1165/rcmb.2013-0016oc
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发表时间：
2013
影响因子：
6.4
通讯作者：
Caughey,GeorgeH
中科院分区：
文献类型：
--
作者：
Xu,Xiang;Greenland,John;Baluk,Peter;Adams,Alicia;Bose,Oishee;McDonald,DonaldM;Caughey,GeorgeH
组织蛋白酶L（Ctsl）是一种被提出的用于控制许多疾病状态中的炎症反应的治疗靶点。然而，Ctsl被认为通过其参与抗原呈递途径来支持宿主防御。假设Ctsl有助于对抗细菌感染，我们研究了它在肺支原体感染小鼠中作为急性和慢性感染性气道炎症模型的作用。在Ctsl −/−和Ctsl +/+小鼠中比较气道接种支原体的反应。感染后，与Ctsl +/+小鼠相比，Ctsl−/−小鼠表现出更多的体重减轻，更高的死亡率（分别为22%和0%），以及更重的肺，但支气管淋巴结较小。感染3天后，Ctsl −/−小鼠肺中活支原体的负荷是Ctsl +/+小鼠的247倍。Ctsl−/−小鼠表现出更严重的肺炎和富含支原体的气道阻塞性渗出物，其发展速度比Ctsl +/+小鼠更快。与Ctsl +/+小鼠感染后显著的淋巴管重塑相比，Ctsl −/−小鼠几乎没有淋巴管生成，但血管重塑和组织炎症同样严重。血液中支原体反应性IgM、伊加和IgG的滴度与Ctsl +/+小鼠相似。然而，酶联免疫吸附斑点试验显示，细胞IFN-γ对支原体抗原的反应显著降低。这些发现表明，Ctsl通过支持淋巴管生成和对感染的细胞免疫应答来帮助遏制支原体感染，并且我们的发现预测，Ctsl的治疗性抑制可以增加支原体感染的严重程度。
Cathepsin L (Ctsl) is a proposed therapeutic target to control inflammatory responses in a number of disease states. However, Ctsl is thought to support host defense via its involvement in antigen presentation pathways. Hypothesizing that Ctsl helps combat bacterial infection, we investigated its role inMycoplasma pulmonis–infected mice as a model of acute and chronic infectious airway inflammation. Responses to the airway inoculation of mycoplasma were compared inCtsl−/−andCtsl+/+mice. After infection,Ctsl−/−mice demonstrated more body weight loss, greater mortality (22% versus 0%, respectively), and heavier lungs thanCtsl+/+mice, but had smaller bronchial lymph nodes. The burden of live mycoplasma in lungs was 247-fold greater inCtsl−/−mice than inCtsl+/+mice after infection for 3 days.Ctsl−/−mice exhibited more severe pneumonia and neutrophil-rich, airway-occlusive exudates, which developed more rapidly than inCtsl+/+mice. Compared with the conspicuous remodeling of lymphatics after infection inCtsl+/+mice, little lymphangiogenesis occurred inCtsl−/−mice, but blood vessel remodeling and tissue inflammation were similarly severe. Titers of mycoplasma-reactive IgM, IgA, and IgG in blood in response to live and heat-killed organisms were similar to those inCtsl+/+mice. However, enzyme-linked immunosorbent spot assays revealed profound reductions in the cellular IFN-γ response to mycoplasma antigen. These findings suggest that Ctsl helps contain mycoplasma infection by supporting lymphangiogenesis and cellular immune responses to infection, and our findings predict that the therapeutic inhibition of Ctsl could increase the severity of mycoplasmal infections.