Mou Rong, Cui Xuan-Yin, Luo Yu-Si, Cheng Yi, Luo Qing-Yuan, Zhang Zhen-Fen, Wu Wen-Lan, Li Jin-Fu, Zhang Ke
The Guizhou Key Laboratory of Microbio and Infectious Disease Prevention & Control/The Key and Characteristic Laboratory of Modern Pathogenicity Biology, Departments of Parasitology & Histology and Embryology, School of Basic Medical Sciences, Guizhou Medical University, Room 220, E-1 Building, Ankang Avenue No. 6, Guiyang, 561113, China.
Emergency ICU, The Affiliated Hospital of Guizhou Medical University, Guiyang, 550004, China.
Parasit Vectors. 2025 Mar 11;18(1):100. doi: 10.1186/s13071-025-06719-w.
Hosts typically elicit diverse immune responses to the infection of various parasitic worms, with intestinal epithelial cells playing pivotal roles in detecting parasite invasion. Hymenolepis nana (H. nana) is a zoonotic parasitic worm that resides in the host's intestine. The contribution and underlying mechanisms of tuft cell-mediated immune reactions against H. nana remain unexplored.
This study endeavors to examine the immune responses in the mouse intestine elicited by the adult H. nana and its excretory-secretory products (ESP). Ileal tissue alteration was detected using hematoxylin and eosin (H&E) staining, changes in the number of intestinal stem cells, goblet cells, tuft cells, and Paneth cells were detected by immunohistochemistry (IHC), immunofluorescence (IF), etc., and changes in the expression of type 2 cytokines and FOXM1 were detected by Western blotting (WB) or real-time quantitative polymerase chain reaction (RT-qPCR).
The presence of adult H. nana and its ESP enhanced the number of tuft cells and goblet cells while fostering the production of type 2 cytokines. Furthermore, the surge in Paneth cells and FOXM1 triggered by H. nana aids in maintaining intestinal stem cells homeostasis and proliferation. Notably, the FOXM1 inhibitor RCM-1 dampened intestinal stem cells differentiation and type 2 cytokines secretion, potentially impeding the host's capacity to eliminate H. nana.
The adult H. nana and its ESP stimulate the immune responses in mice through tuft/interleukin (IL)-13 and FOXM1 signaling pathways and promote the elimination of H. nana from the host through the differentiation of intestinal stem cells into tuft cells, goblet cells, and Paneth cells, as well as the activation of type 2 immune responses. Meanwhile, RCM-1 inhibits the immune responses to H. nana in mice, thus affecting the excretion of H. nana by host.
宿主通常会对各种寄生虫感染引发多种免疫反应，其中肠道上皮细胞在检测寄生虫入侵方面发挥着关键作用。微小膜壳绦虫（Hymenolepis nana，简称H. nana）是一种寄生于宿主体内肠道的人畜共患寄生虫。簇细胞介导的针对微小膜壳绦虫的免疫反应的作用及潜在机制仍未得到探索。
本研究致力于检测成年微小膜壳绦虫及其排泄分泌产物（ESP）在小鼠肠道中引发的免疫反应。采用苏木精-伊红（H&E）染色检测回肠组织变化，通过免疫组织化学（IHC）、免疫荧光（IF）等方法检测肠道干细胞、杯状细胞、簇细胞和潘氏细胞数量的变化，并通过蛋白质免疫印迹法（WB）或实时定量聚合酶链反应（RT-qPCR）检测2型细胞因子和叉头框蛋白M1（FOXM1）表达的变化。
成年微小膜壳绦虫及其ESP的存在增加了簇细胞和杯状细胞的数量，同时促进了2型细胞因子的产生。此外，微小膜壳绦虫引发的潘氏细胞和FOXM1的增加有助于维持肠道干细胞的稳态和增殖。值得注意的是，FOXM1抑制剂RCM-1抑制了肠道干细胞的分化和2型细胞因子的分泌，可能会阻碍宿主清除微小膜壳绦虫的能力。
成年微小膜壳绦虫及其ESP通过簇细胞/白细胞介素（IL）-13和FOXM1信号通路刺激小鼠的免疫反应，并通过肠道干细胞分化为簇细胞、杯状细胞和潘氏细胞以及激活2型免疫反应来促进宿主清除微小膜壳绦虫。同时，RCM-1抑制小鼠对微小膜壳绦虫的免疫反应，从而影响宿主对微小膜壳绦虫的排泄。
