Dietary environmental factors shape the immune defence againstCryptosporidiuminfection

Abstract

SUMMARYCryptosporidiumis a leading cause of diarrheal-related deaths in children, especially in resource-poor settings. It also targets the immunocompromised, chronically infecting people living with HIV and primary immunodeficiencies. There is no vaccine or effective treatment. While it is known from human cases and animal models that CD4+T-cells play a role in curbingCryptosporidium, the role of CD8+cells remains to be defined. Using aCryptosporidium tyzzerimouse model, we show that gut-resident CD8+intraepithelial lymphocytes (IELs) confer resistance to parasite growth. CD8+IELs express, and are dependent on, the ligand-dependent transcription factor aryl hydrocarbon receptor (AHR). AHR deficiency reduced CD8+IELs, decreased their cytotoxicity, and worsened infection. Transfer of CD8+IELs rescued severely immunodeficient mice from death followingCryptosporidiumchallenge. Finally, dietary supplementation of the AHR pro-ligand indole-3-carbinol to new-born mice promoted resistance to infection. Therefore, common dietary metabolites augment the host immune response to cryptosporidiosis, protecting against disease.