Cell https://doi.org/10.1016/j.cell.2018.07.016 (2018)

What drives symptomatic or asymptomatic infections remains unclear. In Cell, Sanchez et al. investigate the inter-individual, non-genetic variation factors that influence the course of infection. Among mice infected with a 50% lethal dose of the enteric pathogen Citrobacter rodentium, healthy infected mice show enrichment for genes involved in iron metabolism in the liver, relative to the expression of such genes in morbid mice, but these mice have similar pathogen loads. Dietary iron protects mice against mortality and gut pathology after infection with doses 1–1,000 times higher than the 100% lethal dose and suppresses the expression of genes involved in C. rodentium’s virulence. Dietary iron limits glucose absorption, induces insulin resistance and increases glucose availability in the intestine, which is sufficient for the suppression of virulence-factor-encoding genes, independently of the microbiota. In the long term, dietary iron drives the selection of attenuated strains of C. rodentium that establish commensalism.