Abstract
BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.