Ryan Pardy

Cryptosporidium spp. are Apicomplexan parasites that infect intestinal epithelial cells (IEC) and are a significant cause of diarrheal disease (cryptosporidiosis). In 2013, the Global Enterics Multicenter Study (GEMS) identified Cryptosporidium as second only to rotavirus as a cause of severe diarrhea and death in infancy in sub-Saharan Africa and Southern Asia. Symptoms last 1-2 weeks in immune-competent individuals; however, in individuals with suppressed T cell responses (e.g., organ transplant recipients or patients with acquired immunodeficiency syndrome [AIDS]), chronic infection can spread to the bile ducts and liver and become life-threatening. In addition, the anti-cryptosporidial drug Nitazoxanide is not approved in Canada and does not work in immunocompromised individuals, underscoring the need to better understand immune control of Cryptosporidium by IEC.

Previous studies have identified the crucial role of interferon-gamma (IFN-γ) in control of parasite replication and T cells in parasite clearance. My recent studies used single-cell RNA-sequencing, microscopy, and flow cytometry to understand the impact of IFN-γ and Cryptosporidium infection on IEC and the dynamics of parasite control following IFN-γ stimulation. In particular, we showed that IFN-γ acts on uninfected IEC to limit parasite dissemination, in part because IEC exhibit a delayed responsiveness to IFN-γ relative to immune cells.

Research in my lab will combine these techniques with intestinal organoids, 3D cultures that mimic the natural conditions of IEC and enable studies of primary IEC. We will use these tools to study the interplay between types I, II, and III IFN during infection with Cryptosporidium and how these signals are regulated by intestinal epithelial cells.