Cryptosporidium is 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. Although it is known from human cases and animal models that CD4⁺ T cells play a role in curbing Cryptosporidium, the role of CD8⁺ T cells remains to be defined. Using a Cryptosporidium tyzzeri mouse model, we show that gut-resident CD8⁺ intraepithelial lymphocytes (IELs) confer resistance to parasite growth. CD8⁺ IELs express and depend on the ligand-dependent transcription factor aryl hydrocarbon receptor (AHR). AHR deficiency reduces CD8⁺ IELs, decreases their cytotoxicity, and worsens infection. Transfer of CD8⁺ IELs rescues severely immunodeficient mice from death following Cryptosporidium challenge. Finally, dietary supplementation of the AHR pro-ligand indole-3-carbinol in newborn mice promotes resistance to infection. Therefore, common dietary metabolites augment the host immune response to cryptosporidiosis, protecting against disease.

隐孢子虫是儿童腹泻相关死亡的主要原因，特别是在资源匮乏的环境中。它还针对免疫功能低下、长期感染艾滋病毒和原发性免疫缺陷的人。没有疫苗或有效的治疗方法。尽管从人类病例和动物模型中已知 CD4 ⁺ T 细胞在抑制隐孢子虫方面发挥作用，但 CD8 ⁺ T 细胞的作用仍有待确定。使用泰氏隐孢子虫小鼠模型，我们发现肠道驻留的 CD8 ⁺ 上皮内淋巴细胞 (IEL) 具有对寄生虫生长的抵抗力。 CD8 ⁺ IEL 表达并依赖配体依赖性转录因子芳基烃受体 (AHR)。 AHR 缺陷会降低 CD8 ⁺ IEL，降低其细胞毒性，并使感染恶化。 CD8 ⁺ IEL 的转移可挽救隐孢子虫攻击后严重免疫缺陷的小鼠免于死亡。最后，在新生小鼠中膳食补充 AHR 前配体吲哚-3-甲醇可促进对感染的抵抗力。因此，常见的饮食代谢物可增强宿主对隐孢子虫病的免疫反应，从而预防疾病。