Enteric Tuft Cell Responses and Host-Microbial Dynamics During Giardia muris Infection

Sosnowski, Olivia Stefania

Enteric Tuft Cell Responses and Host-Microbial Dynamics During Giardia muris Infection

dc.contributor.advisor	Buret, Andre
dc.contributor.author	Sosnowski, Olivia Stefania
dc.contributor.committeemember	Hirota, Simon
dc.contributor.committeemember	McKay, Derek
dc.date	2024-11
dc.date.accessioned	2024-09-20T18:54:08Z
dc.date.available	2024-09-20T18:54:08Z
dc.date.issued	2024-09-18
dc.description.abstract	Enteric tuft cells constitute an important aspect of the host response to intestinal parasites. Tuft cells detect and respond to enteric parasites, secreting molecules such as IL-25, leading to the expansion of tuft and goblet cells to ultimately promote parasite clearance. The intestinal protozoan parasite Giardia disrupts the intestinal environment and leads to impaired barrier function. Infection is also associated with altered microbiota composition and function. This study characterised the tuft cell response in the murine small intestine after G. muris infection, identifying tuft and goblet cell hyperplasia during the clearance phase (day 21). G. muris infected mice also displayed increased expression of genes defining secretory epithelial cells (Aoth1), tuft cell-related genes (Dclk1, Tas2r130, Tas2r), and goblet cell-related genes (Muc2, Klf4) during early infection (day 4 and day 11). Increases in cell number and many of the changes in gene expression during G. muris infection were observed at both the site of active Giardia colonization (jejunum) and more distally (ileum). Tuft cell-deficient (Pou2f3-/-) mice had a lower trophozoite burden compared to wild-type (C57Bl/6) mice during early infection, demonstrating that tuft cells help facilitate G. muris colonization. To investigate other contributors to the tuft cell-Giardia crosstalk, the microbiota was considered since microbial derived products can modify tuft cell functions, Giardia can cause microbiota dysbiosis, and the microbiota can influence Giardia colonization. A fecal microbiota transplantation (FMT) using microbiota from naïve C57Bl/6 or Pou2f3-/- donors revealed that FMT from Pou2f3-/- donors prior to G. muris infection resulted in a lower parasite load than in mice that received FMT from C57Bl/6 donors, illustrating that the microbiota influences G. muris colonization. Upon evaluating if Giardia-modified microbiota (GMM) could elicit a tuft cell response, transplantation with small intestinal GMM 11 days after infection did not lead to changes in tuft or goblet cell number, thus the mechanism through which Giardia engages tuft cells requires further exploration. Collectively, this study characterises the tuft cell response to Giardia, identifies a novel role for tuft cells in promoting Giardia colonization, and provides insights into how the microbiota contributes to the dynamics between enteric tuft cells and parasitic infections.
dc.identifier.citation	Sosnowski, O. S. (2024). Enteric tuft cell responses and host-microbial dynamics during Giardia muris infection (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.
dc.identifier.uri	https://hdl.handle.net/1880/119825
dc.language.iso	en
dc.publisher.faculty	Science
dc.publisher.institution	University of Calgary
dc.rights	University of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.
dc.subject	Giardia
dc.subject	Protozoan
dc.subject	Tuft cells
dc.subject	Microbiome
dc.subject	Microbiota
dc.subject.classification	Biology--Cell
dc.subject.classification	Microbiology
dc.subject.classification	Parasitology
dc.title	Enteric Tuft Cell Responses and Host-Microbial Dynamics During Giardia muris Infection
dc.type	doctoral thesis
thesis.degree.discipline	Biological Sciences
thesis.degree.grantor	University of Calgary
thesis.degree.name	Doctor of Philosophy (PhD)
ucalgary.thesis.accesssetbystudent	I do not require a thesis withhold – my thesis will have open access and can be viewed and downloaded publicly as soon as possible.