Young Scientist Award

Anisakiasis is an accidental zoonosis caused by consuming raw fish parasitized with infective Anisakis spp third stage larvae (L3). Severe symptoms may include mucosal ulcers, granulomas and chronic inflammation in the gastro-intestinal tract, features potentially linked to tumorigenesis. A novel aspect of Anisakis biology involves the release of extracellular vesicles (EVs), potential players in host-parasite dynamics and disease progression. This study explores, for the first time, immunomodulatory and potential tumorigenic effects of Anisakis EVs on 2D human intestinal organoids (HIO), an innovative model mirroring gut epithelial during human infection. 470 Anisakis spp. L3 were collected from fish visceral cavities and cultured in RPMI 1640 in 1x P/S at 37°C with 5% CO2 for 24h. EVs were isolated using Exoquick kit and characterized through Nanoparticle Tracking Analyses (NTA), Interferometric Nanoparticle Analysis (iNTA), an innovative technique never used on helminths EVs, and electron microscopy (SEM, TEM). HIO were exposed to Anisakis EVs for 48h, followed by analyses of gene expression and cytokines amounts using comparative transcriptomics, qRT-PCR and Luminex assay. Treating HIO with 2.92 x 109 particles/cells altered several transcripts with a potential involvement in tumorigenesis. Significant downregulation of EPHB2 and LEFTY1 and upregulation of NUPR1, genes associated with colorectal cancer, was observed. Additionally, a reduction in specific mediators of inflammation and cell cycle regulation like IL-33R, CD40, CEACAM-1, IL-1b, GM-CSF, IL-15 and IL-23 was detected, supporting the suggested parasite’s immunomodulatory effect on the accidental human host, aiding Anisakis to establish and persist in its niche