State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Clinical Laboratory Center, Tumor Hospital Affiliated to Xinjiang Medical University, Urumqi, Xinjiang 830011, China.
Xinjiang Medical University Affiliated Traditional Chinese Medicine Hospital, Xinjiang, China.
Int Immunopharmacol. 2024 Apr 20;131:111808. doi: 10.1016/j.intimp.2024.111808. Epub 2024 Mar 7.
The pathogen of alveolar echinococcosis (AE) is Echinococcus multilocularis (E. multilocularis), which has the characteristics of diffuse infiltration and growth and has a high mortality rate. At present, the role of macrophages in AE infection has attracted more and more attention, but the new biomarkers and polarization mechanisms of macrophages are rarely studied. In this study, CIBERSORT and WGCNA algorithms were used to establish a weighted gene co-expression network, and MTLN was identified as a biological marker of M2-type macrophages, which participated in energy metabolism of macrophages and mediated inflammatory response, but the role of MTLN in AE was not studied. In this study, liver tissue samples from AE patients were collected and immunofluorescence co-localization showed the relationship between MTLN and macrophage distribution. E. multilocularis infected mouse model was established to analyze the expression of MTLN, liver fibrosis, and inflammatory reaction after E. multilocularis infection. The cell experiment simulated the liver microenvironment of E. multilocularis infected human body and analyzed the expression of MTLN by QRT-PCR and western blot in vitro. The data showed that liver fibrosis occurred in AE patients, and MTLN was activated near the focus. After E. multilocularis infected mice, the expression of MTLN increased with time. In the cell experiment, after the antigen of E. multilocularis protoscolex stimulated normal liver cells, the expression of MTLN increased 48 h, at this time, M2 was up-regulated and M1 was down-regulated. Therefore, MTLN may be the key gene to regulate the polarization of M2 macrophages and cause fibrosis.
泡型包虫病（AE）的病原体是多房棘球绦虫（E.multilocularis），其具有弥散浸润性生长的特点，致死率较高。目前，巨噬细胞在 AE 感染中的作用越来越受到关注，但对巨噬细胞的新型标志物和极化机制研究较少。本研究采用 CIBERSORT 和 WGCNA 算法构建加权基因共表达网络，鉴定 MTLN 为 M2 型巨噬细胞的生物标志物，参与巨噬细胞的能量代谢，并介导炎症反应，但 MTLN 在 AE 中的作用尚未研究。本研究收集 AE 患者的肝组织样本，免疫荧光共定位显示 MTLN 与巨噬细胞分布的关系。建立多房棘球蚴感染小鼠模型，分析感染后 MTLN、肝纤维化和炎症反应的表达。细胞实验模拟人感染多房棘球蚴的肝脏微环境，通过 QRT-PCR 和 Western blot 体外分析 MTLN 的表达。结果表明，AE 患者发生肝纤维化，MTLN 在病灶附近激活。多房棘球蚴感染小鼠后，MTLN 随时间表达增加。在细胞实验中，多房棘球蚴原头节抗原刺激正常肝细胞后，MTLN 在 48 h 表达增加，此时 M2 上调，M1 下调。因此，MTLN 可能是调节 M2 型巨噬细胞极化并导致纤维化的关键基因。
