The Impact of Genetic Background and resolved infection with Trichuris muris on the enteric nervous system in mice

Abstract

Introduction The gastrointestinal tract is so extensively innervated that it has been referred to as the 'mini brain' and can function independently of central nervous system control. It is also well known that there is a bidirectional link between the immune system and the nervous system that can affect response to pathogenic invasion. Despite the potential importance of the neuro-immune link in susceptibility to gut disease, the impact of host genetics and resolved infection on the enteric neural map is poorly understood. We investigated these factors using two mouse strains with known differences in peripheral nervous innervation (AKR and C57BL/6) and resolved infection with a Th1 or Th2 immune profile in the resistant C57BL/6 strain following infection with a high (Th2) or low (Th1) dose of Trichuris muris. Materials and Methods We measured gross and microscopic anatomical features, such as gut length and muscle thickness, faecal pellet parameters such as number, weight, length, water content and transit time, and neuroreceptor expression, to examine differences between groups in gut physiology. Enteric neuronal density was quantified using histological and immunohistochemical techniques. Due to potential impact on neuronal cell survival, enteric glial cell number and NOS expression was quantified in infection groups. Results We identified significant differences in gut transit time, faecal pellet length and enteric neuronal density between AKR and C57BL/6 mouse strains. We also identified significant differences in transit time, faecal water content and enteric neuronal density in C57BL/6 mice following resolution of infection. Conclusion Results suggest that genetic background and resolved infection affect gut physiology and enteric neuronal density. This may be reflected in a human population affecting susceptibility to and recovery from infection-driven pathology.

Date of Award	1 Aug 2018
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Jaleel Miyan (Supervisor) & Joanne Pennock (Supervisor)