Ledesma-Soto Yadira, Chávez-Soto Ilse, Calderón-Torres Marissa, Rodríguez-Lozoya Andrea Monserrat, Olguin Jonadab E, Hernández-Portilla Luis B, Flores-Ortíz César M, Candanedo Fernando, Rodriguez-Sosa Miriam, Hernández-Navia Sonia E, Terrazas Luis I
Facultad de Estudios Superiores Iztacala, Unidad de Investigación en Biomedicina, Universidad Nacional Autónoma de México, Tlalnepantla, Edo. México, 54090, México.
Facultad de Estudios Superiores Iztacala, Laboratorio Nacional en Salud, Universidad Nacional Autónoma de México, Tlalnepantla, Edo. México, 54090, México.
Inflammopharmacology. 2025 Jun 27. doi: 10.1007/s10787-025-01821-y.
Ulcerative colitis (UC) is a chronic inflammatory disease that is increasing in prevalence worldwide. Notably, helminth infections, known for their immunoregulatory properties, are inversely related to inflammatory conditions such as UC. Research has indicated that Taenia crassiceps infection can improve inflammatory-mediated diseases, including type 1 diabetes, experimental autoimmune encephalomyelitis, and colitis. Subsequent studies revealed that helminth-derived products can replicate the effects of complete infection in the context of inflammatory diseases; however, the mechanisms underlying these effects remain unclear. This study examined the impact of intact glycans from T. crassiceps excreted/secreted products (TcES) on host responses to dextran sodium sulfate (DSS)-induced colitis.
UC was induced by administering 4% DSS in the drinking water for 9 days. The mice were treated with intact TcES, glycan-depleted TcES, or protein-depleted TcES 2 days after colitis induction. Symptoms of the disease, along with immunologic and histopathological evaluations, were performed.
Colitic mice that received intact TcES presented fewer disease symptoms and less histopathological damage. Intact TcES reduced the proinflammatory response while increasing the production of IL-4, IL-22, IL-31, and MCP-1 and promoting M2 macrophage polarization via PD-L2 expression. Furthermore, intact TcES diminished neutrophil infiltration, inhibited NF-κB and p38 phosphorylation in the colon, and suppressed reactive oxygen species and 3-nitrotyrosine levels, thus protecting the colon. These effects were accompanied by increased expression of E-cadherin and β-catenin, indicating improved epithelial barrier integrity. Conversely, mice treated with glycan-depleted or protein-depleted TcES exhibited exacerbated colitis characterized by disruption of colon tissue architecture, extensive inflammation, and epithelial damage, including loss of E-cadherin and β-catenin and a lack of M2 macrophage polarization.
Glycoconjugates on TcES play a significant role in mediating the immunomodulatory effects that alleviate DSS-induced colitis.
溃疡性结肠炎（UC）是一种慢性炎症性疾病，在全球范围内的患病率呈上升趋势。值得注意的是，以免疫调节特性著称的蠕虫感染与UC等炎症性疾病呈负相关。研究表明，肥胖带绦虫感染可改善炎症介导的疾病，包括1型糖尿病、实验性自身免疫性脑脊髓炎和结肠炎。随后的研究表明，蠕虫衍生产品在炎症性疾病中可复制完全感染的效果；然而，这些效果背后的机制仍不清楚。本研究考察了肥胖带绦虫排泄/分泌产物（TcES）中的完整聚糖对宿主对葡聚糖硫酸钠（DSS）诱导的结肠炎反应的影响。
通过在饮用水中给予4% DSS 9天诱导UC。在结肠炎诱导2天后，用完整的TcES、聚糖缺失的TcES或蛋白质缺失的TcES对小鼠进行治疗。对疾病症状以及免疫和组织病理学评估进行了检测。
接受完整TcES的结肠炎小鼠表现出较少的疾病症状和较轻的组织病理学损伤。完整的TcES降低了促炎反应，同时增加了IL-4、IL-22、IL-31和MCP-1的产生，并通过PD-L2表达促进M2巨噬细胞极化。此外，完整的TcES减少了中性粒细胞浸润，抑制了结肠中NF-κB和p38的磷酸化，并抑制了活性氧和3-硝基酪氨酸水平，从而保护了结肠。这些作用伴随着E-钙黏蛋白和β-连环蛋白表达的增加，表明上皮屏障完整性得到改善。相反，用聚糖缺失或蛋白质缺失的TcES治疗的小鼠表现出结肠炎加重，其特征为结肠组织结构破坏、广泛炎症和上皮损伤，包括E-钙黏蛋白和β-连环蛋白的丧失以及M2巨噬细胞极化的缺乏。
TcES上的糖缀合物在介导减轻DSS诱导的结肠炎的免疫调节作用中起重要作用。
