Allergenic Shrimp Tropomyosin Distinguishes from a Non-Allergenic Chicken Homolog by Pronounced Intestinal Barrier Disruption and Downstream Th2 Responses in Epithelial and Dendritic Cell (Co)Culture

• Published in: Nutrients Vol. 16; no. 8; p. 1192
• Main Authors: Zuurveld, Marit, Ogrodowczyk, Anna M, Benedé, Sara, Czolk, Rebecca, Lucia Bavaro, Simona, Randow, Stefanie, Markiewicz, Lidia H, Wróblewska, Barbara, Molina, Elena, Kuehn, Annette, Holzhauser, Thomas, Willemsen, Linette E M
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 17.04.2024; MDPI
• Subjects: Allergens; Allergens - immunology; Animals; Caco-2 Cells; Cell culture; Chickens; Coculture Techniques; Cytokines; Cytokines - metabolism; Cytotoxicity; Dendritic cells; Dendritic Cells - drug effects; Dendritic Cells - immunology; Dendritic Cells - metabolism; epithelial barrier; Epithelial Cells - drug effects; Epithelial Cells - immunology; Epithelial Cells - metabolism; Flow cytometry; Food allergies; food allergy; Food science; HT29 Cells; Humans; Intestinal Mucosa - immunology; Intestinal Mucosa - metabolism; Lymphocytes; mucosal immunology; Ovalbumin; Penaeidae - immunology; Penicillin; Pore size; Proteins; R&D; Research & development; sensitizing allergenicity; Th2 Cells - immunology; Tropomyosin - immunology; tropomyosins; New York; United States > US; mucosal immunology; tropomyosins; epithelial barrier; food allergy; sensitizing allergenicity
• ISSN: 2072-6643; 2072-6643
• DOI: 10.3390/nu16081192

Tropomyosins (TM) from vertebrates are generally non-allergenic, while invertebrate homologs are potent pan-allergens. This study aims to compare the risk of sensitization between chicken TM and shrimp TM through affecting the intestinal epithelial barrier integrity and type 2 mucosal immune activation. Epithelial activation and/or barrier effects upon exposure to 2-50 μg/mL chicken TM, shrimp TM or ovalbumin (OVA) as a control allergen, were studied using Caco-2, HT-29MTX, or HT-29 intestinal epithelial cells. Monocyte-derived dendritic cells (moDC), cocultured with HT-29 cells or moDC alone, were exposed to 50 μg/mL chicken TM or shrimp TM. Primed moDC were cocultured with naïve Th cells. Intestinal barrier integrity (TEER), gene expression, cytokine secretion and immune cell phenotypes were determined in these human in vitro models. Shrimp TM, but not chicken TM or OVA exposure, profoundly disrupted intestinal barrier integrity and increased alarmin genes expression in Caco-2 cells. Proinflammatory cytokine secretion in HT-29 cells was only enhanced upon shrimp TM or OVA, but not chicken TM, exposure. Shrimp TM enhanced the maturation of moDC and chemokine secretion in the presence or absence of HT-29 cells, while only in the absence of epithelial cells chicken TM activated moDC. Direct exposure of moDC to shrimp TM increased IL13 and TNFα secretion by Th cells cocultured with these primed moDC, while shrimp TM exposure via HT-29 cells cocultured with moDC sequentially increased IL13 expression and IL4 secretion in Th cells. Shrimp TM, but not chicken TM, disrupted the epithelial barrier while triggering type 2 mucosal immune activation, both of which are key events in allergic sensitization.