Translocation of nanoparticles and Mycobacterium marinum across the intestinal epithelium in zebrafish and the role of the mucosal immune system

• Published in: Developmental and comparative immunology 2017-02, Vol.67, p.508-518
• Main Authors: Løvmo, Signe Dille, Speth, Martin Tobias, Repnik, Urska, Koppang, Erling Olaf, Griffiths, Gareth Wyn, Hildahl, Jon Paul
• Format: Article
• Language: English
• Subjects: Animals; Antigen Presentation; Antigen sampling; Antigens; Aquaculture; Bacteria; Bacterial Translocation - immunology; Biological Transport; Cells, Cultured; Danio rerio; Drug delivery; Drug Delivery Systems; Enterocytes - immunology; Epithelial cells; Epithelium; Fish Diseases - immunology; Fluorescence; Immune response; Immune system; Immunity, Mucosal; Immunosuppressive agents; Intestinal Mucosa - microbiology; Intestinal Mucosa - physiology; Intestine; Intubation; Leukocytes; Liver; Localization; Macrophages; Microorganisms; Microparticles; Mucosal immunity; Mycobacterium Infections, Nontuberculous - immunology; Mycobacterium marinum; Mycobacterium marinum - physiology; Nanoparticles; Nanoparticles - metabolism; Spleen; Transendothelial and Transepithelial Migration; Translocation; Vaccines; Zebrafish; Zebrafish - immunology
• ISSN: 0145-305X; 1879-0089
• DOI: 10.1016/j.dci.2016.06.016

Nano- and microparticles are promising carrier systems for oral delivery of drugs or vaccines, particularly in fish aquaculture. However, the mechanisms of uptake, trans-epithelial transport and immune response to nano/micrometer sized particles, or microorganisms such as bacteria are poorly understood in fish. Here, adult zebrafish were used to study the uptake of different nano- and microparticles and the pathogenic bacteria Mycobacterium marinum in the intestine, and their interactions with epithelial cells and the mucosal immune system. Fluorescent particles or bacteria were delivered directly into the adult zebrafish intestine by oral intubation and their localization was imaged in intestine, liver and spleen sections. Zebrafish do not appear to have M-cells, but both nanoparticles and bacteria were rapidly taken up in the intestine and transported to the liver and spleen. In each tissue, both bacteria and particles largely localized to leukocytes, presumably macrophages. •Zebrafish antigen sampling enterocytes functionally but not morphologically resemble mammalian M-cells.•Nanoparticles rapidly cross the zebrafish intestine and accumulate in lymphoid organs.•Antigen sampling enterocytes are an entry point for Mycobacterium marinum infection.