Maruszewska-Cheruiyot Marta, Szewczak Ludmiła, Krawczak-Wójcik Katarzyna, Kierasińska Magdalena, Stear Michael, Donskow-Łysoniewska Katarzyna
Department of Experimental Immunotherapy, Faculty of Medicine, Lazarski University, Świeradowska 43, 02-662 Warsaw, Poland.
Department of Parasitology, Institute of Functional Biology and Ecology, Faculty of Biology, University of Warsaw, Miecznikowa 1, 00-096 Warsaw, Poland.
Int J Mol Sci. 2023 Sep 15;24(18):14127. doi: 10.3390/ijms241814127.
Parasitic nematodes and their products are promising candidates for therapeutics against inflammatory bowel diseases (IBD). Two species of nematodes, the hookworm and the whipworm , are being used in clinical treatment trials of IBD referred to as "helminth therapy". is a well-known model for human hookworm infections. Excretory-secretory (ES) products of L4 stage that developed during colitis show a different immunomodulatory effect compared to the ES of from healthy mice. The aim of the study was to evaluate excretory-secretory proteins produced by L4 stage males and females that developed in the colitic milieu. Mass spectrometry was used to identify proteins. Blast2GO was used to investigate the functions of the discovered proteins. A total of 387 proteins were identified in the ES of L4 males (HpC males), and 330 proteins were identified in the ES of L4 females that developed in the colitic milieu (HpC females). In contrast, only 200 proteins were identified in the ES of L4 males (Hp males) and 218 in the ES of L4 females (Hp females) that developed in control conditions. Most of the proteins (123) were detected in all groups. Unique proteins identified in the ES of HpC females included annexin, lysozyme-2, apyrase, and galectin. Venom allergen/Ancylostoma-secreted protein-like, transthyretin-like family proteins, and galectins were found in the secretome of HpC males but not in the secretome of control males. These molecules may be responsible for the therapeutic effects of nematodes in DSS-induced colitis.
寄生线虫及其产物有望成为治疗炎症性肠病（IBD）的候选药物。两种线虫，钩虫和鞭虫，正被用于IBD的临床试验，即“蠕虫疗法”。是人类钩虫感染的著名模型。与健康小鼠的ES相比，在结肠炎期间发育的L4期的排泄分泌（ES）产物显示出不同的免疫调节作用。本研究的目的是评估在结肠炎环境中发育的L4期雄性和雌性产生的排泄分泌蛋白。采用质谱法鉴定蛋白质。使用Blast2GO研究发现蛋白质的功能。在L4雄性（HpC雄性）的ES中总共鉴定出387种蛋白质，在结肠炎环境中发育的L4雌性（HpC雌性）的ES中鉴定出330种蛋白质。相比之下，在对照条件下发育的L4雄性（Hp雄性）的ES中仅鉴定出200种蛋白质，在L4雌性（Hp雌性）的ES中鉴定出218种蛋白质。大多数蛋白质（123种）在所有组中均被检测到。在HpC雌性的ES中鉴定出的独特蛋白质包括膜联蛋白、溶菌酶-2、腺苷三磷酸双磷酸酶和半乳糖凝集素。在HpC雄性的分泌组中发现了毒液过敏原/钩虫分泌蛋白样、转甲状腺素蛋白样家族蛋白和半乳糖凝集素，而在对照雄性的分泌组中未发现。这些分子可能是线虫对葡聚糖硫酸钠诱导的结肠炎具有治疗作用的原因。
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