Key discoveries from research in anisakiasis: From parasite biology to pathology in the human host.

Anisakidosis is a fish-borne zoonosis characterised by mild to severe gastrointestinal (GI) symptoms and potentially linked to the onset of allergic reactions and cancer. The disease follows the ingestion of marine products infected with third-stage (L3) larvae of the genera Anisakis and Phocanema. Epidemiologically, anisakiasis is most prevalent in countries where fish consumption is high, such as Japan and the Mediterranean regions; however, the globalization of dietary habits has contributed to the expansion of its incidence worldwide. In this Chapter, we provide an overview of aspects related to the disease, from the description of the biological features of L3 and fourth-stage (L4) larvae, to the mechanisms likely responsible for allergic reactions and GI lesions. Multiple factors contribute to the allergenicity of Anisakis spp., including exposure time, GI and endolysosomal stability and antigenic structure. A growing body of research focuses on the parasite excretory/secretory (E/S) products, including extracellular vesicles, encompassing proteolytic enzymes, immunomodulatory molecules, and potential virulence factors. E/S products play key roles in host–parasite interactions, such as tissue invasion, immune evasion, and allergic sensitization. Both in vivo and in vitro studies (conducted in murine models of infection and human epithelial and dendritic cell cultures, respectively) have enhanced current understanding of anisakidosis pathophysiology, elucidating mechanisms of mucosal damage, cytokine production, and adaptive immune responses. These models also offer insights into chronic disease outcomes, that include formation of eosinophilic granulomas, chronic abdominal pain, and a potential correlation between anisakidosis and the occurrence of a tumorigenic microenvironment in the GI tract.