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 Humanities > Biological Sciences > Biochemistry Biological Sciences > Immunology Humanities > 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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