The intestinal parasite Cryptosporidium, transmitted through water sources, is one of the leading diarrheal diseases worldwide. It can be a serious threat, causing malnutrition or even death in infants and young children and can also cause great harm in those with compromised immune systems.
Currently there is no vaccine or effective treatment, in part because mouse models of the disease are insufficient. This is because the parasite strain that infects humans is not good at infecting mice so researchers have had to rely on mice with defective immune systems.
Now, however, researchers from the University of Pennsylvania have developed a model of infection that affects immunologically normal mice using CRISPR-Cas9 gene editing. Details of their findings appear in Cell Host & Microbe.
To develop their model, researchers first identified a form of Cryptosporidium that commonly affects mice. The team then sequenced and annotated that genome, finding it to be extremely close to its human-infecting relative. From there, they began manipulating the genome with CRISPR, which included introducing a gene to make the parasite glow so they could track infection.
Tracking this parasite as it infected laboratory mice, the team was able to determine that T cells and the protein interferon-gamma were both critical in the body’s defense against the parasite.
"We now have a fantastic mouse model that mirrors the human disease," says Boris Striepen, a biologist at Penn Vet and senior author on the study. "It's a powerful lab model, where we can introduce changes at will and test the importance of different components of the immune response to infection, which is just what we need to develop an effective vaccine."
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Introducing mice to an experimental vaccine containing a weakened version of the parasite protected them from infection equally as well as mice that had experienced full infection. The team is continuing research into the pathways involved in conferring protection against Cryptosporidium and sharing the model in hopes that others will make new discoveries about the disease.'
Image: A section of intestine from an infected mouse shows Cryptosporidium tyzzeri parasites in red. Image courtesy of Muthgapatti Kandasamy, Adam Sateriale, and Boris Striepen.