Cryptosporidiuminfection of human small intestinal epithelial cells induces type III interferon and impairs infectivity of Rotavirus

Abstract

ABSTRACTCryptosporidiosis is a major cause of severe diarrheal disease in infants from resource poor settings. The majority of infections are caused by the human-specific pathogenC. hominisand absence of in vitro growth platforms has limited our understanding of host-pathogen interactions and development of effective treatments. To address this problem, we developed a stem cell-derived culture system forC. hominisusing human enterocytes differentiated under air-liquid interface (ALI) conditions. Human ALI cultures supported robust growth and complete development ofC. hominisin vitro including all life cycle stages.C. hominisinfection induced a strong interferon response from enterocytes, likely driven by an endogenous dsRNA virus in the parasite. Prior infection withCryptosporidiuminduced type III IFN secretion and consequently blunted infection with Rotavirus, including live attenuated vaccine strains. The development of hALI provides a platform for further studies on human-specific pathogens, including clinically important coinfections that may alter vaccine efficacy.