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The parasite Cryptosporidia infects and completes its entire life cycle within the intestinal epithelium. It has been long appreciated that interferon gamma is critical for protection, but the source of this cytokine, the mechanism of induction and the cell site of action have been unknown. Here Gullicksrud et al.1 demonstrate in a mouse model that interferon gamma regulation and protection center on the infected epithelial cell. The work is of importance for the fundamental advances it provides on mucosal defense from intracellular parasitism, as well as providing a foundation for the advancement of vaccination against this cause of diarrhea, malnutrition and death of infants in low and middle income countries.