Investigation of the evolutionary link between the enteric neuronal system and immune system using the early vertebrate species Danio rerio
File(s)
Author(s)
Wenz, Ralf
Type
Thesis
Abstract
Neuroimmunology in healthy homeostasis has recently attracted attention, especially in the brain. The intestine, in contrast, and its neuroimmunological interactions are much overlooked. While models regarding how neuroimmune similarities have been put forward, there is a gap as to why and when neuroimmune interactions in the intestine might have arisen.
To fill this gap, I herein put forward a theoretical framework postulating that intestinal neuroimmune interactions have arisen in early vertebrates, thus allowing the sensing and expelling of pathogens from the intestine via peristalsis. Immune cells, I postulate, sense the pathogens and signal to neurons to increase intestinal peristalsis, expelling pathogens from the intestine; thus leading to higher survival rates.
Using the early vertebrate species Danio rerio (zebrafish), I show that there is tantalising but tentative evidence that exposure to lysed Mycobacterium marinum increases peristalsis of the intestinal bulb, hinting at the possibility of the existence of a mechanism that expels pathogens from the intestine via peristalsis. Besides this main finding, I also established new and needed baseline readings of intestinal peristalsis. These new readings show the vital importance of accurately controlling for ambient temperature and anaesthetic concentration during measurements. Moreover, I demonstrate that macrophages are important for regular homeostatic peristalsis of the intestine in the early vertebrate Danio rerio, like the mammalian counterpart, the mouse. In order to achieve the above results, several new pieces of equipment and methods had to be developed. Firstly, I developed the Multiscope, a system of multiple microscopes combined that allow the imaging of many specimens simultaneously at controlled temperatures for long periods of time in an affordable manner. By building four Multiscopes from simple and cheap components I was able to acquire in one month the data that would have, using conventional equipment, required an entire year. Further, I established a fast, easy and early procedure to identify transparent mutant zebrafish, by which an estimated 60,000 animals could be saved worldwide every year (Wenz et al., 2020).
To fill this gap, I herein put forward a theoretical framework postulating that intestinal neuroimmune interactions have arisen in early vertebrates, thus allowing the sensing and expelling of pathogens from the intestine via peristalsis. Immune cells, I postulate, sense the pathogens and signal to neurons to increase intestinal peristalsis, expelling pathogens from the intestine; thus leading to higher survival rates.
Using the early vertebrate species Danio rerio (zebrafish), I show that there is tantalising but tentative evidence that exposure to lysed Mycobacterium marinum increases peristalsis of the intestinal bulb, hinting at the possibility of the existence of a mechanism that expels pathogens from the intestine via peristalsis. Besides this main finding, I also established new and needed baseline readings of intestinal peristalsis. These new readings show the vital importance of accurately controlling for ambient temperature and anaesthetic concentration during measurements. Moreover, I demonstrate that macrophages are important for regular homeostatic peristalsis of the intestine in the early vertebrate Danio rerio, like the mammalian counterpart, the mouse. In order to achieve the above results, several new pieces of equipment and methods had to be developed. Firstly, I developed the Multiscope, a system of multiple microscopes combined that allow the imaging of many specimens simultaneously at controlled temperatures for long periods of time in an affordable manner. By building four Multiscopes from simple and cheap components I was able to acquire in one month the data that would have, using conventional equipment, required an entire year. Further, I established a fast, easy and early procedure to identify transparent mutant zebrafish, by which an estimated 60,000 animals could be saved worldwide every year (Wenz et al., 2020).
Version
Open Access
Date Issued
2021-05
Date Awarded
2022-02
Copyright Statement
Creative Commons Attribution NonCommercial Licence
License URL
Advisor
Dallman, Margaret
Sponsor
Imperial College London
Publisher Department
Department of Life Sciences
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)