Institute of Immunology, Department of Veterinary Medicine, Freie Universität Berlin, Berlin, Germany.
Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Biochemistry, Shared Facility for Mass Spectrometry, Berlin, Germany.
J Immunol Res. 2021 Nov 25;2021:6234836. doi: 10.1155/2021/6234836. eCollection 2021.
Immunomodulation of airway hyperreactivity by excretory-secretory (ES) products of the first larval stage (L1) of the gastrointestinal nematode is reported by us and others. Here, we aimed to identify the proteins accounting for the modulatory effects of the L1 ES proteins and studied six selected L1 proteins for their immunomodulatory efficacy in a murine OVA-induced allergic airway disease model. In particular, an enzymatically active chitinase mediated amelioration of clinical signs of airway hyperreactivity, primarily associated with suppression of eosinophil recruitment into the lung, the associated chemokines, and increased numbers of RELM interstitial lung macrophages. While there is no indication of chitinase directly interfering with dendritic cell activation or antigen presentation to CD4 T cells, treatment of allergic mice with the worm chitinase influenced the hosts' own chitinase activity in the inflamed lung. The three-dimensional structure of the chitinase as determined by high-resolution X-ray crystallography revealed high similarities to mouse acidic mammalian chitinase (AMCase) but a unique ability of chitinase to form dimers. Our data indicate that the structural similarities between the parasite and host chitinase contribute to the disease-ameliorating effect of the helminth-derived chitinase on allergic lung inflammation.
我们和其他人已经报道过，胃肠道线虫的第一幼虫期（L1）的排泄-分泌（ES）产物可调节气道高反应性。在这里，我们旨在确定导致 L1 ES 蛋白调节作用的蛋白，并在小鼠 OVA 诱导的过敏性气道疾病模型中研究六种选定的 L1 蛋白的免疫调节功效。特别地，一种具有酶活性的几丁质酶介导了气道高反应性临床症状的改善，主要与嗜酸性粒细胞向肺内募集的抑制、相关趋化因子以及 RELM 间质肺巨噬细胞数量的增加有关。虽然没有迹象表明几丁质酶直接干扰树突状细胞的激活或抗原呈递给 CD4 T 细胞，但用蠕虫几丁质酶处理过敏小鼠会影响宿主在发炎肺中的自身几丁质酶活性。通过高分辨率 X 射线晶体学确定的几丁质酶的三维结构显示出与鼠酸性哺乳动物几丁质酶（AMCase）的高度相似性，但几丁质酶形成二聚体的独特能力。我们的数据表明，寄生虫和宿主几丁质酶之间的结构相似性有助于寄生虫衍生的几丁质酶对过敏性肺炎症的疾病改善作用。
