Grant: CIHR Fellowship

Cryptosporidium parasites infect epithelial cells (ECs) in the gastrointestinal (GI) tract and can cause severe diarrhea. This infection can be fatal in individuals with a compromised immune system, such as organ transplant recipients, while infections in children are associated with growth defects, reduced cognitive development and death. Current research indicates that long-term, protective immunity against Cryptosporidium is possible, suggesting that vaccine development is an important strategy to prevent infection. However, current small animal models fail to replicate important aspects of human infection and this has limited our ability to study the immune response to Cryptosporidium, thereby hampering vaccine development. To address this knowledge gap, my research will use a recently identified murine strain of Cryptosporidium that is highly similar to human strains genetically and in terms of pathogenesis. This strain was used to demonstrate that an immune molecule called interferon-gamma (IFN-gamma) is crucial for controlling Cryptosporidium infection. My research project will aim to determine how ECs responding to IFN-gamma become resistant to Cryptosporidium. I hypothesize that IFN-gamma has this effect by activating anti-parasitic responses within ECs, and by increasing the rate of EC turnover to help shed infected cells. Within the intestine, EC precursors begin at the base of the intestinal villi, and as they develop and mature, they "ride the elevator" to the villus tip, where they die and are released into the intestinal lumen. By speeding up the EC elevator, infected cells may be released before they are able to spread the infection to healthy cells. Together, my work will improve our understanding of how IFN-gamma contributes to protective immunity against Cryptosporidium infection and provide new insights into how normal, physiological processes like the EC elevator can be used to combat this and other intestinal infections.