Browsing by Author "Sosnowski, Olivia Stefania"

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    Enteric Tuft Cell Responses and Host-Microbial Dynamics During Giardia muris Infection
    (2024-09-18) Sosnowski, Olivia Stefania; Buret, Andre; Hirota, Simon; McKay, Derek
    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.