Publication highlights

Researchers have mapped the human metabolic pathways that Cryptosporidium, an intestinal parasite, requires to survive. They conducted a genome-scale screening experiment that involves systematically disabling nearly every protein-coding gene, individually, from human intestinal cells, before infecting the cells with Cryptosporidium. The team found that genes involved in making cholesterol appeared to have opposing effects - some boosting infection and others blocking it. This balance hinged on a molecule midway through the cholesterol production line, squalene. This molecule protects against oxidative stress by stimulating the production of glutathione, which Cryptosporidium needs but cannot make. This leaves the parasite dependent on glutathione from the host cell, a dependency which can be targeted with a high cholesterol drug called lapaquistat. This drug reduced infection in a mouse model of disease and completely blocked intestinal damage, suggesting it could be repurposed to fight Cryptosporidium.

Researchers at the Francis Crick Institute have discovered that a common dietary supplement could protect against chronic Cryptosporidium infections which are particularly prevalent in children under two and in areas with poorer sanitation. The researchers exposed mice to the Cryptosporidium parasite and observed that infection triggered an expansion of immune cells in the intestinal epithelium, which are part of the first line of defence against the parasite. When these CD8+ T cells were transferred to mice with weakened immune systems, the researchers saw that the mice were now able to fight off Cryptosporidium infection. Mice that lack the AHR receptor, or healthy mice fed a diet specifically deficient in indoles, had a reduced population of intestinal CD8+ T cells. This meant the mice were less able to fight off the infection, and showed that CD8+ T cells are reliant on the AHR system to protect the intestine.