Something secreted by bacteria in the intestines of mice helps them resist influenza virus infection in their lungs, according to a new study. This protection is reversed when the mice are given broad-spectrum antibiotics. Andreas Wack of the Francis Crick Institute, who led the research, says his team is trying to figure out what this bacterial signal is. What they know is that it doesn’t affect immune cells, but rather the epithelial cells lining the lungs (Cell Rep. 2019, DOI: 10.1016/j.celrep.2019.05.105). The signal seems to help maintain a low but responsive level of a viral defense mechanism built into these epithelial cells, which would likely encounter flu viruses first. The defense mechanism is led by interferon proteins that bind to receptors on the surface of epithelial cells, leading to a boost in production and release of antiviral proteins. Mice given antibiotics, which knock down levels of gut microbes, were more susceptible to flu infection than animals not treated with antibiotics. But the ability to resist the flu returned when the researchers performed a fecal transplant in the antibiotic-treated mice from donors that had not received antibiotics. Wack says that flu resistance is just one example—any virus that infects the lungs would be subject to this gut-lung interplay.