The Role of Intestinal Tuft Cells in the Murine Response to Infection with the Cestode, Hymenolepis diminuta
Date
2023-12-21
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Abstract
The small intestinal tuft cell has garnered considerable interest in the field of parasitic immunology over the past few years for being a sentinel cell in the host response against nematode, trematode, and protist parasites. The tuft cell displays versatility in its capacity to respond to various luminal stimuli and in the mediators it produces. Whether the tuft cell is involved in the host response to enteric cestodes has not been previously explored. My thesis seeks to determine if enteric tuft cells coordinate host anti-helminthic immunity against cestode parasites using murine infection with Hymenolepis diminuta as a model system. H. diminuta-infection induced tuft cell hyperplasia in mice which is dependent on IL-4R𝛼 signalling and the adaptive immune system. Tuft cell hyperplasia still occurs in germ free mice, indicating that the parasite and host responses to the parasite and not microbial factors drive tuft cell hyperplasia. Using pou2f3-/- tuft cell-deficient mice, our study reveals that enteric tuft cells modulate local host responses to H. diminuta that are ultimately important in quicker worm expulsion from the mouse. At the same time, tuft cell deficiency does not abrogate the development of systemic immunity against H. diminuta, nor the ultimate (albeit delayed) expulsion of the worms. We further show that although infection with H. diminuta induces both tuft cell hyperplasia as well as protection from subsequent parasitic infection with H. bakeri, the tuft cell is not solely responsible for mediating systemic and other local Th2 responses against H. diminuta. This work reveals that while tuft cells play subtle roles in fine tuning the host response against the parasite H. diminuta, tuft cell deficiency is overcome by redundancies that exist in host’s mucosal immune arsenal leading to ultimate expulsion of the parasite.
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Keywords
cestode, tuft cell, helminth, Th2 immunity
Citation
Rajeev, S. (2023). The role of intestinal tuft cells in the murine response to infection with the cestode, Hymenolepis diminuta (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.