Protective Immunity in a Genetically Tractable Natural Mouse Model of Cryptosporidiosis

Cryptosporidium is a leading cause of diarrheal disease and an important contributor to early childhood mortality, malnutrition, and growth faltering. Older children in high endemicity regions appear resistant to infection, while previously unexposed adults remain susceptible as documented by large outbreaks in the United States. Experimental studies in humans and animals support the development of disease resistance, but we do not understand the mechanisms that underlie protective immunity to Cryptosporidium. Here we isolate parasites from naturally infected wild mice to derive a model of Cryptosporidium infection in immunocompetent C57BL/6 mice. Both parasite and host are genetically tractable in this model which facilitates mechanistic investigation and rational vaccine design. Similar to human cryptosporidiosis, this infection causes intestinal pathology, and interferon-γ controls early infection while T-cells are critical for clearance. Importantly, mice that controlled a primary infection were resistant to secondary challenge, and an attenuated vaccine provided protection equal to live infection.