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Mycotoxins - an analysis of their immunomodulatory effects and methods for their detection

Loftus, Jonathan (2018) Mycotoxins - an analysis of their immunomodulatory effects and methods for their detection. PhD thesis, Dublin City University.

Abstract
Mycotoxins are toxic secondary fungal metabolites which contaminate a variety of food and feed products and pose serious health risks to humans and animals. Exposure to even low concentrations of these toxins can result in chronic diseases, with immunosuppressive and carcinogenic effects being of greatest concern. They are estimated to be found in 25% of the world’s food supply and have huge economic consequences globally. There is a lack of understanding of how mycotoxins interact with the immune system. The purpose of this research was to increase this understanding by examining the cytotoxic and immunomodulatory effects of the mycotoxins patulin, DON, ZEN and T-2 toxin in vitro, using the murine macrophage cell line, J774A.1. The results clearly demonstrated that T-2 toxin and ZEN significantly affect cell viability at high concentrations while sub-lethal concentrations of patulin, DON, ZEN and T-2 toxin, alone and in combinations, had a significant effect on host defence functions, through deregulation of IL-6, IL-10, IL-27, IL-12p40, IL-1β and TNF-α cytokine production, phagocytosis, and the cell surface expression of CD80, CD86, TLR4 and MHCII. The effects of these toxins are dependent on concentrations and combinations. This knowledge should be taken into consideration in the implementation of detection limits, aimed at minimising risks to human and animal health from mycotoxin exposure. A possible solution to this was explored through the use of a novel microfluidic technology, Lab-in-a-Trench, which demonstrated the ability to measure the immunomodulatory effects of mycotoxin combinations in ‘real-time’. Increased awareness of the hazards presented by mycotoxins has also led to the need for rapid detection systems. Recombinant antibodies incorporated into sensitive immunoassays offers the ability to satisfy this need. This thesis describes optimisation of immune library production for the mycotoxins patulin, ochratoxin A and aflatoxin M1 using an avian host. Immune libraries were generated and screened for all three targets and a scFv clone capable of binding AFM1 was successfully isolated using phage display technology in a depletion bio-panning process. The incorporation of recombinant antibodies with high sensitivity into rapid and inexpensive detection systems coupled with a novel method of determining immunomodulatory effects of mycotoxin combinations would allow early intervention, thus improving global food safety and providing significant cost savings to the agri-food sector.
Metadata
Item Type:Thesis (PhD)
Date of Award:November 2018
Refereed:No
Supervisor(s):Loscher, Christine and O'Kennedy, Richard
Subjects:Biological Sciences > Biochemistry
Biological Sciences > Immunology
DCU Faculties and Centres:DCU Faculties and Schools > Faculty of Science and Health > School of Biotechnology
Use License:This item is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 3.0 License. View License
ID Code:22614
Deposited On:22 Nov 2018 15:59 by Christine Loscher . Last Modified 30 Jul 2021 12:46
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