• Simon Gagnon, Faculty of Veterinary Medicine, Université de Montréal
• Ana Ibarra-Menses, Faculty of Veterinary Medicine, Université de Montréal
• Francis Beaudry, Faculty of Veterinary Medicine, Université de Montréal
• David Langlais, Department of Human Genetics, McGill University Genome Centre | 5Department of Microbiology and Immunology, McGill Research Centre on Complex Traits
• Mélanie Dieudé, Université de Montréal | Canadian Donation and Transplant Research Program (CDTRP) | Héma-Québec, Montréal
• Christopher Fernandez-Prada, Faculty of Veterinary Medicine, Université de Montréal | Department of Microbiology and Immunology, McGill Research Centre on Complex Traits

Diarrheal disease is the most common cause of illness in North America and worldwide, being the second leading cause of death in children under five years of age, according to the WHO. Giardia duodenalis is a zoonotic agent frequently isolated, with a high burden of disease, ranking in the top three provincially and nationally reported enteric infections. Of note, recent studies have found that long-term Giardia infections, which are not monitored in immunosuppressed patients, cause several intestinal and extraintestinal sequelae related to an altered immune system.

In this context, our project aims to study the relationship between the immune response and the parasitic infection in immunosuppressed patients following transplantation. We hypothesize that infection by G. duodenalis, either before or after organ transplant could impact the immune response of the patient, leading to an increase in the risk of graft rejection.

To better understand the impact of this parasite and evaluate our hypothesis, we have set two main aims: i) to evaluate the impact of Giardia (inflammation, antiparasitic response, maintenance of the integrity of the epithelia barrier and control of oxidative stress) on a co-culture of intestinal Caco-2 cells and Giardia, in the absence and the presence of mycophenolate mofetil (MMF); ii) to determining the potential mechanism of toxicity of MMF by analyzing the proteomic meltome of Caco-2 cells and Giardia in the presence of this drug.

Our results could lead to the implementation of novel practices in parasite detection in patients, as well as to modification of immunosuppressive strategies.