Norovirus inflames the stomach and/or intestines and causes pain, nausea, vomiting, and diarrhea. It is super contagious and kills tens of thousands of people each year. But until now, we did not even know which cells it targets to create all this havoc. A recent study by a public-private consortium working in universities and Genetech has just discovered the elusive cell type (in mice): they’re called tuft cells, and they reside in the ilium and colon.
Obviously, norovirus attacks intestinal epithelial cells, the specialized cells that line tubes within the body. But last year, the same group reported that noroviruses would infect only a rare subset of them and not most of their neighbors. But the researchers could not discern what made these select cells so special.
They knew that norovirus used a particular receptor to infect cells and that this receptor is both necessary and sufficient for infection. Oddly, the receptor is an immunoregulator thought to be expressed by blood-forming cells, specifically immune progenitor cells in the bone marrow. These could make their way to the intestines once they mature. But mice that got bone marrow transplants that lacked this receptor were still susceptible to norovirus infection, so that’s clearly not the case.
Instead, it now turns out that these isolated intestinal cells infected by norovirus express this very immune receptor, which had never been seen in epithelial cells before. They turned out to be tuft cells, named for the long tuft they sport, which extend into the intestine like truffula trees from . Aside from their tuft, these cells are known for making IL-25, a cytokine that coordinates the immune response to tapeworms and other parasites.
IL-25 stimulates the growth of the tuft cells that produce it, which explains the observation that infection with parasites augments norovirus infection. The parasite induces IL-25 production, which expands the population of tuft cells, which in turn expands the available opportunities for norovirus infection.
Work done in 2015, also in mice, showed that treatment with broad spectrum antibiotics that ablate intestinal bacteria will prevent norovirus infection. This led the researchers who performed it to reasonably conclude that the microbiome is required for norovirus infection. But in the new study, sterile, germ-free mice were infected just fine. This turned out to be because the antibiotics also diminished the numbers of tuft cells in the colon; only they, and not commensal bacteria, are required for norovirus infection.
Since norovirus infection can elicit inflammatory-bowel-disease-like symptoms and it acts through tuft cells, the authors wonder if maybe tuft cells are responsible for inflammatory bowel disease. It’s also possible that other viruses infect tuft cells. To understand further, we’ll have to figure out why harming these cells can produce such a dramatic and potentially fatal collection of symptoms.