Anisakis infection induces IgE responses resulting from ILC2 and Th2 cell activation via IL-33 in the murine stomach.

Anisakis simplex, a parasitic nematode transmitted through the consumption of raw or undercooked seafood, is known to cause gastric anisakidosis, often accompanied by acute inflammatory and allergic responses. However, the underlying immunological mechanisms remain poorly understood. In this study, we established a murine model by orally infecting BALB/c mice with live Anisakis larvae to elucidate the host immune response. Repeated infection with live Anisakis larvae, but not with homogenates, induced severe gastric inflammation, accompanied by a marked elevation of total IgE, Anisakis-specific IgE, Ani s 1-specific IgE, and interleukin (IL)-5 in the serum. Active cutaneous anaphylaxis confirmed the presence of functional Anisakis-specific IgE capable of mediating immediate hypersensitivity. Flow cytometry of gastric lamina propria cells showed increased infiltration of IL-5 producing group 2 innate lymphoid cells (ILC2s), eosinophils, IL-4 producing T helper (Th) cells and B cells in mice with repeated infection. Furthermore, immunohistochemistry revealed widespread localization of IL-33-positive cells in the gastric mucosa, consistent with the observed increased levels of truncated IL-33 and total IL-33. These findings suggest that Anisakis infection induces a type 2 immune response through IL-33-driven activation of ILC2s followed by Th2 development, thereby promoting eosinophilia and antigen-specific IgE. This model enables new insights of Anisakis-associated allergic inflammation and may serve as future therapeutic studies.